Search

Lee Shettle,1 Eugene McLaurin,2 Joseph Martel,3 John W Seaman III,4 Georges Weissgerber5 1Shettle Eye Research, Inc, Largo, FL, USA; 2Total Eye Care, Memphis, TN, USA; 3Research Center, Martel Eye Medical Group, Rancho Cordova, CA, USA; 4Novartis Pharmaceuticals Corporation, Fort Worth, TX, USA; 5Novartis Institutes for Biological Research, Basel, SwitzerlandCorrespondence: Lee Shettle, Shettle Eye Research, Inc, Largo, FL, USA, Tel +1 727-674-2500, Fax +1 727-674-2550, Email lshettle@yahoo.com Eugene McLaurin, Total Eye Care, Memphis, TN, USA, Tel +1-912-441-2128, Email emclaurin6@aol.comPurpose: To assess the efficacy, safety, and pharmacokinetics of new topical ocular anti-TNFα antibody fragment licaminlimab in the relief of persistent ocular discomfort in severe dry eye disease (DED).Patients and Methods: Patients with ≥ 6-month history of DED, regular use of artificial tears, and best-corrected visual acuity (BCVA) of ≥ 55 letters in each eye (Early Treatment Diabetic Retinopathy Score) at baseline were included in this multicenter, randomized, vehicle-controlled, double masked study. A total of 514 patients were screened. After a 2-week run-in with Vehicle, all qualifying patients received Vehicle eye drops for 4 weeks. Patients with global ocular discomfort score ≥ 50 at the end of this 4-week period were randomized to receive licaminlimab (60 mg/mL ophthalmic solution) (69 patients) or Vehicle (65 patients) for 6 weeks. The primary efficacy endpoint was change from baseline in global ocular discomfort score at Day 29. Safety assessments included adverse events and ophthalmology examination including intraocular pressure (IOP). Serum licaminlimab levels were also determined.Results: Change from baseline to Day 29 in global ocular discomfort score was statistically significantly greater for licaminlimab than for Vehicle (p = 0.041). No safety issues were identified. Serum licaminlimab was undetectable in most patients; the maximum concentration observed was 8.47 ng/mL.Conclusion: Topical ocular licaminlimab demonstrated statistically significant improvement in global ocular discomfort score compared to Vehicle in patients with severe DED, with good tolerability, no increase in IOP, and minimal systemic drug exposure.Keywords: anti-tumor necrosis factor α, dry eye disease, single-chain antibody fragment, topical treatment

Ten soil cores were collected from the long-term heavy metal-contaminated Savannah River Site (SRS) and studied using shotgun metagenomics. In-line with our previous reports, Bradyrhizobium spp. dominated the SRS soils, and thus we recommend that SRS bioremediation studies target the Bradyrhizobium genus., Competing Interests: The authors declare no conflict of interest.

Radiologic usual interstitial pneumonia (UIP) patterns and concordant clinical characteristics define a diagnosis of idiopathic pulmonary fibrosis (IPF). However, limited expert access and high inter-clinician variability challenge early and pre-invasive diagnostic sensitivity and differentiation of IPF from other interstitial lung diseases (ILDs). We investigated a machine learning-driven software system, Fibresolve, to indicate IPF diagnosis in a heterogeneous group of 300 patients with interstitial lung disease work-up in a retrospective analysis of previously and prospectively collected registry data from two US clinical sites. Fibresolve analyzed cases at the initial pre-invasive assessment. An Expert Clinical Panel (ECP) and three panels of clinicians with varying experience analyzed the cases for comparison. Ground Truth was defined by separate multi-disciplinary discussion (MDD) with the benefit of surgical pathology results and follow-up. Fibresolve met both pre-specified co-primary endpoints of sensitivity superior to ECP and significantly greater specificity ( p = 0.0007) than the non-inferior boundary of 80.0%. In the key subgroup of cases with thin-slice CT and atypical UIP patterns ( n = 124), Fibresolve's diagnostic yield was 53.1% [CI: 41.3-64.9] (versus 0% pre-invasive clinician diagnostic yield in this group), and its specificity was 85.9% [CI: 76.7-92.6%]. Overall, Fibresolve was found to increase the sensitivity and diagnostic yield for IPF among cases of patients undergoing ILD work-up. These results demonstrate that in combination with standard clinical assessment, Fibresolve may serve as an adjunct in the diagnosis of IPF in a pre-invasive setting.

Background: Survivors of critical illness experience high rates of serious health-related suffering. The delivery of palliative care may assist in decreasing this burden for survivors and their families. Objectives: To understand beliefs, attitudes, and experiences of post-intensive care unit (ICU) program clinicians regarding palliative care and explore barriers and facilitators to incorporating palliative care into critical illness survivorship care. Design: Qualitative inquiry using semistructured interviews and framework analysis. Results were mapped using the Consolidated Framework for Implementation Research. Setting/Subjects: We interviewed 29 international members (United States, United Kingdom, Canada) of the Critical and Acute Illness Recovery Organization post-ICU clinic collaborative. Results: All interprofessional clinicians described components of palliative care as essential to post-ICU clinic practice, including symptom management, patient/family support, facilitation of goal-concordant care, expectation management and anticipatory guidance, spiritual support, and discussion of future health care wishes and advance care planning. Facilitators promoting palliative care strategies were clinician level, including first-hand experience, perceived value, and a positive attitude regarding palliative care. Clinician-level barriers were reciprocals and included insufficient palliative care knowledge, lack of self-efficacy, and a perceived need to protect ICU survivors from interventions the clinician felt may adversely affect recovery or change the care trajectory. System-level barriers included time constraints, cost, and lack of specialty palliative care services. Conclusion: Palliative care may be an essential element of post-ICU clinic care. Implementation efforts focused on tailoring strategies to improve post-ICU program clinicians' palliative care knowledge and self-efficacy could be a key to enhanced care delivery for survivors of critical illness.

Background: The new noninvasive Vitalstream (VS) continuous physiological monitor (Caretaker Medical LLC, Charlottesville, Virginia), allows continuous cardiac output by a low pump-inflated, finger cuff that pneumatically couples arterial pulsations via a pressure line to a pressure sensor for detection and analysis. Physiological data are communicated wirelessly to a tablet-based user interface via Bluetooth or Wi-Fi. We evaluated its performance against thermodilution cardiac output in patients undergoing cardiac surgery., Methods: We compared the agreement between thermodilution cardiac output to that obtained by the continuous noninvasive system during cardiac surgery pre and post-cardiac bypass. Thermodilution cardiac output was performed routinely when clinically indicated by an iced saline cold injectate system. All comparisons between VS and TD/CCO data were post-processed. In order to match the VS CO readings to the averaged discrete TD bolus data, the averaged CO readings of the ten seconds of VS CO data points prior to a sequence of TD bolus injections was matched. Time alignment was based on the medical record time and the VS time-stamped data points. The accuracy against reference TD measurements was assessed via Bland-Altman analysis of the CO values and standard concordance analysis of the ΔCO values (with a 15% exclusion zone)., Results: Analysis of the data compared the accuracy of the matched measurement pairs of VS and TD/CCO VS absolute CO values with and without initial calibration to the discrete TD CO values, as well as the trending ability, i.e., ΔCO values of the VS physiological monitor compared to those of the reference. The results were comparable with other non-invasive as well as invasive technologies and Bland-Altman analyses showed high agreement between devices in a diverse patient population. The results are significant regarding the goal of expanding access to effective, wireless and readily implemented fluid management monitoring tools to hospital sections previously not covered because of the limitations of traditional technologies., Conclusion: This study demonstrated that the agreement between the VS CO and TD CO was clinically acceptable with a percent error (PE) of 34.5 to 38% with and without external calibration. The threshold for an acceptable agreement between the VS and TD was considered to be below 40% which is below the threshold recommended by others., (© 2023. The Author(s).)

Background: Robot-assisted bronchoscopy (RAB) is among the newest bronchoscopic technologies, allowing improved visualization and access for small and hard-to-reach nodules. RAB studies have primarily been conducted at academic centers, limiting the generalizability of results to the broader real-world setting, while variability in diagnostic yield definitions has impaired the validity of cross-study comparisons. The objective of this study was to determine the diagnostic yield and sensitivity for malignancy of RAB in patients with pulmonary lesions in a community setting and explore the impact of different definitions on diagnostic yield estimates., Methods: Data were collected retrospectively from medical records of patients ≥ 21 years who underwent bronchoscopy with the Monarch® Platform (Auris Health, Inc., Redwood City, CA) for biopsy of pulmonary lesions at three US community hospitals between January 2019 and March 2020. Diagnostic yield was calculated at the index RAB and using 12-month follow-up data. At index, all malignant and benign (specific and non-specific) diagnoses were considered diagnostic. After 12 months, benign non-specific cases were considered diagnostic only when follow-up data corroborated the benign result. An alternative definition at index classified benign non-specific results as non-diagnostic, while an alternative 12-month definition categorized index non-diagnostic cases as diagnostic if no malignancy was diagnosed during follow-up., Results: The study included 264 patients. Median lesion size was 19.3 mm, 58.9% were peripherally located, and 30.1% had a bronchus sign. Samples were obtained via Monarch in 99.6% of patients. Pathology led to a malignant diagnosis in 115 patients (43.6%), a benign diagnosis in 110 (41.7%), and 39 (14.8%) non-diagnostic cases. Index diagnostic yield was 85.2% (95% CI: [80.9%, 89.5%]) and the 12-month diagnostic yield was 79.4% (95% CI: [74.4%, 84.3%]). Alternative definitions resulted in diagnostic yield estimates of 58.7% (95% CI: [52.8%, 64.7%]) at index and 89.0% (95% CI: [85.1%, 92.8%]) at 12 months. Sensitivity for malignancy was 79.3% (95% CI: [72.7%, 85.9%]) and cancer prevalence was 58.0% after 12 months., Conclusions: RAB demonstrated a high diagnostic yield in the largest study to date, despite representing a real-world community population with a relatively low prevalence of cancer. Alternative definitions had a considerable impact on diagnostic yield estimates., (© 2023. The Author(s).)

Objective: To examine the needs of adult survivors of critical illness through a lens of palliative care., Research Methodology: A qualitative study of adult survivors of critical illness using semi-structured interviews and framework analysis., Setting: Participants were recruited from the post-intensive care unit clinic of a mid-Atlantic academic medical center in the United States., Findings: Seventeen survivors of critical illness aged 34-80 (median, 66) participated in the study. The majority of patients were female (64.7 %, n = 11) with a median length of index ICU stay of 12 days (interquartile range [IQR] 8-19). Interviews were conducted February to March 2021 and occurred a median of 20 months following the index intensive care stay (range, 13-33 months). We identified six key themes which align with palliative care principles: 1) persistent symptom burden; 2) critical illness as a life-altering experience; 3) spiritual changes and significance; 4) interpreting/managing the survivor experience; 5) feelings of loss and burden; and 6) social support needs., Conclusion: Our findings suggest that palliative care components such as symptom management, goals of care discussions, care coordination, and spiritual and social support may assist in the assessment and treatment of survivors of critical illness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Despite the previous development of criteria for palliative screening tools, there remains a lack of validated and practical screening processes for the general hospitalized patient population for everyday clinical use. This quality improvement project's aim was to implement a practical institution-based adult inpatient palliative care screening tool embedded into the electronic medical record with an automated alert process to assist in identifying patients earlier within hospital admission. The project used a preimplementation and postimplementation design and followed the Plan-Do-Study-Act process to measure the effectiveness of the tool and alert process in decreasing time from admission to palliative care referral and impact on referring patterns. During the project period, 1851 palliative care referrals were completed, and minimal difference (0.6%) was noted in the average time from admission to referral preimplementation and postimplementation ( P = .939). There was a 3.7% increase in referrals postimplementation and a shift in referring service patterns ( P = .321). Although the expected outcome of earlier palliative referrals during admissions was not met, the development and implementation of the tool and alert process is a step toward the creation of a standard practical tool for the general hospitalized patient population., (Copyright © 2023 by The Hospice and Palliative Nurses Association. All rights reserved.)

Purpose: To evaluate a prototype home optical coherence tomography device and automated analysis software for detection and quantification of retinal fluid relative to manual human grading in a cohort of patients with neovascular age-related macular degeneration., Methods: Patients undergoing anti-vascular endothelial growth factor therapy were enrolled in this prospective observational study. In 136 optical coherence tomography scans from 70 patients using the prototype home optical coherence tomography device, fluid segmentation was performed using automated analysis software and compared with manual gradings across all retinal fluid types using receiver-operating characteristic curves. The Dice similarity coefficient was used to assess the accuracy of segmentations, and correlation of fluid areas quantified end point agreement., Results: Fluid detection per B-scan had area under the receiver-operating characteristic curves of 0.95, 0.97, and 0.98 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively. On a per volume basis, the values for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid were 0.997, 0.998, and 0.998, respectively. The average Dice similarity coefficient values across all B-scans were 0.64, 0.73, and 0.74, and the coefficients of determination were 0.81, 0.93, and 0.97 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively., Conclusion: Home optical coherence tomography device images assessed using the automated analysis software showed excellent agreement to manual human grading., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Background: Each year, approximately one million older adults die in American intensive care units (ICUs) or survive with significant functional impairment. Inadequate symptom management, surrogates' psychological distress and inappropriate healthcare use are major concerns. Pioneering work by Dr. J. Randall Curtis paved the way for integrating palliative care (PC) specialists to address these needs, but convincing proof of efficacy has not yet been demonstrated., Design: We will conduct a multicenter patient-randomized efficacy trial of integrated specialty PC (SPC) vs. usual care for 500 high-risk ICU patients over age 60 and their surrogate decision-makers from five hospitals in Pennsylvania., Intervention: The intervention will follow recommended best practices for inpatient PC consultation. Patients will receive care from a multidisciplinary SPC team within 24 hours of enrollment that continues until hospital discharge or death. SPC clinicians will meet with patients, families, and the ICU team every weekday. SPC and ICU clinicians will jointly participate in proactive family meetings according to a predefined schedule. Patients in the control arm will receive routine ICU care., Outcomes: Our primary outcome is patient-centeredness of care, measured using the modified Patient Perceived Patient-Centeredness of Care scale. Secondary outcomes include surrogates' psychological symptom burden and health resource utilization. Other outcomes include patient survival, as well as interprofessional collaboration. We will also conduct prespecified subgroup analyses using variables such as PC needs, measured by the Needs of Social Nature, Existential Concerns, Symptoms, and Therapeutic Interaction scale., Conclusions: This trial will provide robust evidence about the impact of integrating SPC with critical care on patient, family, and health system outcomes., Competing Interests: Conflicts of Interests See relevant ICMJE forms., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Green ash (Fraxinus pennsylvanica) is the most widely distributed ash tree in North America. Once common, it has experienced high mortality from the non-native invasive emerald ash borer (EAB; Agrilus planipennis). A small percentage of native green ash trees that remain healthy in long-infested areas, termed "lingering ash," display partial resistance to the insect, indicating that breeding and propagating populations with higher resistance to EAB may be possible. To assist in ash breeding, ecology and evolution studies, we report the first chromosome-level assembly from the genus Fraxinus for F. pennsylvanica with over 99% of bases anchored to 23 haploid chromosomes, spanning 757 Mb in total, composed of 49.43% repetitive DNA, and containing 35,470 high-confidence gene models assigned to 22,976 Asterid orthogroups. We also present results of range-wide genetic variation studies, the identification of candidate genes for important traits including potential EAB-resistance genes, and an investigation of comparative genome organization among Asterids based on this reference genome platform. Residual duplicated regions within the genome probably resulting from a recent whole genome duplication event in Oleaceae were visualized in relation to wild olive (Olea europaea var. sylvestris). We used our F. pennsylvanica chromosome assembly to construct reference-guided assemblies of 27 previously sequenced Fraxinus taxa, including F. excelsior. Thus, we present a significant step forward in genomic resources for research and protection of Fraxinus species., (© 2021 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Objective: This meta-analysis aimed to determine the effectiveness of non-physician provider-led palliative care (PC) interventions in the management of adults with advanced illnesses on patient-reported outcomes and advance care planning (ACP)., Methods: We included randomised trials and cluster trials published in MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Register of Controlled Trials and ClinicalTrials.gov searched until July 2021 that examined individuals ≥18 years with a diagnosis of advanced, life-limiting illness and received a PC intervention led by a non-physician (nurse, advance practitioner or social worker). Our primary outcome was quality of life (QOL), which was extracted as unadjusted or adjusted estimates and measures of variability. Secondary outcomes included anxiety, depression and ACP., Results: Among the 21 studies (2370 subjects), 13 included patients with cancer, 3 with heart failure, 4 with chronic respiratory disease and 1 with chronic kidney disease. The interventions were diverse and varied with respect to team composition and services offered. For QOL, the standardised mean differences suggested null effects of PC interventions compared with usual care at 1-2 months (0.04; 95% CI=-0.14 to 0.23, n=10 randomised controlled trials (RCTs)) and 6-7 months (0.10; 95% CI=-0.15 to 0.34, n=6 RCTs). The results for anxiety and depression were not significant also. For the ACP, there was a strong benefit for the PC intervention (absolute increase of 0.32% (95% CI=0.06 to 0.57)., Conclusions: In this meta-analysis, PC interventions delivered by non-physician were not associated with improvement in QOL, anxiety or depression but demonstrated an impact on the ACP discussion and documentation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

In the Fall of 2016 a workshop was held which brought together over 50 scientists from the ecological and radiological fields to discuss feasibility and challenges of reintegrating ecosystem science into radioecology. There is a growing desire to incorporate attributes of ecosystem science into radiological risk assessment and radioecological research more generally, fueled by recent advances in quantification of emergent ecosystem attributes and the desire to accurately reflect impacts of radiological stressors upon ecosystem function. This paper is a synthesis of the discussions and consensus of the workshop participant's responses to three primary questions, which were: 1) How can ecosystem science support radiological risk assessment? 2) What ecosystem level endpoints potentially could be used for radiological risk assessment? and 3) What inference strategies and associated methods would be most appropriate to assess the effects of radionuclides on ecosystem structure and function? The consensus of the participants was that ecosystem science can and should support radiological risk assessment through the incorporation of quantitative metrics that reflect ecosystem functions which are sensitive to radiological contaminants. The participants also agreed that many such endpoints exit or are thought to exit and while many are used in ecological risk assessment currently, additional data need to be collected that link the causal mechanisms of radiological exposure to these endpoints. Finally, the participants agreed that radiological risk assessments must be designed and informed by rigorous statistical frameworks capable of revealing the causal inference tying radiological exposure to the endpoints selected for measurement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Metagenomic assessment provides a comprehensive survey of soil microbiota; however, isolation and characterization of functionally relevant microbiota are required prior to their application(s), such as for metal remediation. Toward this end, we report the availability of a culture collection comprising uranium (U)-resistant microbial assemblages (CURMA) to the scientific community., (Copyright © 2020 Agarwal et al.)

The catalytic hydrogel membrane reactor (CHMR) is an interfacial membrane process that uses nano-sized catalysts for the hydrogenation of oxidized contaminants in drinking water. In this study, the CHMR was operated as a continuous-flow reactor using nitrite (NO 2 - ) as a model contaminant and palladium (Pd) as a model catalyst. Using the overall bulk reaction rate for NO 2 - reduction as a metric for catalytic activity, we evaluated the effect of the hydrogen gas (H 2 ) delivery method to the CHMR, the initial H 2 and NO 2 - concentrations, Pd density in the hydrogel, and the presence of Pd-deactivating species. The chemical stability of the catalytic hydrogel was evaluated in the presence of aqueous cations (H + , Na + , Ca 2+ ) and a mixture of ions in a hard groundwater. Delivering H 2 to the CHMR lumens using a vented operation mode, where the reactor is sealed and the lumens are periodically flushed to the atmosphere, allowed for a combination of a high H 2 consumption efficiency and catalytic activity. The overall reaction rate of NO 2 - was dependent on relative concentrations of H 2 and NO 2 - at catalytic sites, which was governed by both the chemical reaction and mass transport rates. The intrinsic catalytic reaction rate was combined with a counter-diffusional mass transport component in a 1-D computational model to describe the CHMR. Common Pd-deactivating species [sulfite, bisulfide, natural organic matter] hindered the reaction rate, but the hydrogel afforded some protection from deactivation compared to a batch suspension. No chemical degradation of the hydrogel structure was observed for a model water (pH > 4, Na + , Ca 2+ ) and a hard groundwater after 21 days of exposure, attesting to its stability under natural water conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Neural networks are increasingly used to assess physiological processes or pathologies, as well as to predict the increased likelihood of an impending medical crisis, such as hypotension., Method: We compared the capabilities of a single hidden layer neural network of 12 nodes to those of a discrete-feature discrimination approach with the goal being to predict the likelihood of a given patient developing significant hypotension under spinal anesthesia when undergoing a Cesarean section (C/S). Physiological input information was derived from a non-invasive blood pressure device (Caretaker [CT]) that utilizes a finger cuff to measure blood pressure and other hemodynamic parameters via pulse contour analysis. Receiver-operator-curve/area-under-curve analyses were used to compare performance., Results: The results presented here suggest that a neural network approach (Area Under Curve [AUC] = 0.89 [p < 0.001]), at least at the implementation level of a clinically relevant prediction algorithm, may be superior to a discrete feature quantification approach (AUC = 0.87 [p < 0.001]), providing implicit access to a plurality of features and combinations thereof. In addition, the expansion of the approach to include the submission of other physiological data signals, such as heart rate variability, to the network can be readily envisioned., Conclusion: This pilot study has demonstrated that increased coherence in Arterial Stiffness (AS) variability obtained from the pulse wave analysis of a continuous non-invasive blood pressure device appears to be an effective predictor of hypotension after spinal anesthesia in the obstetrics population undergoing C/S. This allowed us to predict specific dosing thresholds of phenylephrine required to maintain systolic blood pressure above 90 mmHg.

Researchers seldom look at naked genome assemblies: instead the attributes of DNA sequences are mediated through statistics, annotations and high level summaries. Here we present software that visualizes the bare sequences of whole genome assemblies in a zoomable interface. This can assist in detection of chromosome architecture and contamination by the naked eye through changes in color patterns, in the absence of any other annotation. When available, annotations can be visualized alongside or on top of the naked sequence. Genome alignments can also be visualized, laying two genomes side by side in an alignment and highlighting their differences at nucleotide resolution. FluentDNA gives researchers direct visualization of whole genome assemblies, annotations and alignments, for quality control, hypothesis generation, and communicating results., (Copyright © 2020 Seaman and Buggs.)

Chemical modifications that regulate protein expression at the translational level are emerging as vital components of the cellular stress response. Transfer RNAs (tRNAs) are significant targets for methyl-based modifications, which are catalyzed by tRNA methyltransferases (Trms). Here, Saccharomyces cerevisiae served as a model eukaryote system to investigate the role of 2'-O-ribose tRNA methylation in the cell's response to oxidative stress. Using 2'-O-ribose deletion mutants for trms 3, 7, 13, and 44, in acute and chronic exposure settings, we demonstrate a broad cell sensitivity to oxidative stress-inducing toxicants (i.e., hydrogen peroxide, rotenone, and acetic acid). A global analysis of hydrogen peroxide-induced tRNA modifications shows a complex profile of decreased, or undetectable, 2'-O-ribose modification events in 2'-O-ribose trm mutant strains, providing a critical link between this type of modification event and Trm status post-exposure. Based on the pronounced oxidative stress sensitivity observed for trm7 mutants, we used a bioinformatic tool to identify transcripts as candidates for regulation by Trm7-catalyzed modifications (i.e., enriched in UUC codons decoded by tRNAPheGmAA). This screen identified transcripts linked to diverse biological processes that promote cellular recovery after oxidative stress exposure, including DNA repair, chromatin remodeling, and nutrient acquisition (i.e., CRT10, HIR3, HXT2, and GNP1); moreover, these mutants were also oxidative stress-sensitive. Together, these results solidify a role for TRM3, 7, 13, and 44, in the cellular response to oxidative stress, and implicate 2'-O-ribose tRNA modification as an epitranscriptomic strategy for oxidative stress recovery., Competing Interests: The authors have declared that no competing interests exist.

Adolescents' future aspirations and expectations influence the decisions they make as they transition into adulthood. However, less is known about how specific sociocultural factors interact with the formation of future aspirations and expectations and their association with goal attainment in emerging adulthood. The present study begins to fill this gap by using person-centered analysis with high school students (N = 517; 53% female; 92% white) from a rural county undergoing significant economic transition. Its aim was to identify future orientation profiles based on adolescent-reported future aspirations and expectations for success in both education and career. Four latent profiles were identified and labeled: universally high aspirations and expectations; low college aspirations and expectations; lower aspirations than expectations; and universally low aspirations and expectations. Significant gender differences were found. High school males were less likely to be in the universally high profile and more likely to be in the universally low and low college aspirations and expectations profiles. Future orientation profile placement was associated with differences in adolescent experiences in family, school, and community contexts as well as their work and education status and future residential aspirations in emerging adulthood. The findings inform future research and applied efforts focused on rural youth's preparation for adult roles, and on retaining rural youth, a necessity for the vitality of rural communities.

This article reviews the basic setup and function of surgical navigation and displays a variety of applications in oral and maxillofacial surgery. The use of surgical navigation for dental implant placement is discussed elsewhere in this issue., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Heterogeneous hydrogenation catalysis is a promising approach for treating oxidized contaminants in drinking water, but scale-up has been limited by the challenge of immobilization of the catalyst while maintaining efficient mass transport and reaction kinetics. We describe a new process that addresses this issue: the catalytic hydrogel membrane (CHM) reactor. The CHM consists of a gas-permeable hollow-fiber membrane coated with an alginate-based hydrogel containing catalyst nanoparticles. The CHM benefits from counter-diffusional transport within the hydrogel, where H 2 diffuses from the interior of the membrane and contaminant species (e.g., NO 2 - , O 2 ) diffuse from the bulk aqueous solution. The reduction of O 2 and NO 2 - were investigated using CHMs with varying palladium catalyst densities, and mass transport of reactive species in the catalytic hydrogel was characterized using microsensors. The thickness of the "reactive zone" within the hydrogel affected the reaction rate and byproduct selectivity, and it was dependent on catalyst density. In a continuously mixed flow reactor test using groundwater, the CHM activity was stable for a 3 day period. Outcomes of this study illustrate the potential of the CHM as a scalable process in the treatment of aqueous contaminants.

At the Department of Energy (DOE) managed Savannah River Site (SRS), uranium and other heavy metals continue to pose threats to the ecosystem health and processes. In the oxic soil of this site, uranium is present primarily as soluble salts of the uranyl ion (i.e., U(VI) or UO 2 2+ ). Although UO 2 2+ has a strong sorption to the soil, the mobile indigenous bacteria may facilitate its transport. On the contrary, precipitation of UO 2 2+ with phosphate has been found to be an alternative remediation strategy. This research investigated the effects of mobile bacteria and phytate on UO 2 2+ transport at SRS in column experiments. It was discovered that UO 2 2+ can barely be mobilized by de-ionized water but can be significantly transported with the aid of mobile indigenous bacteria. UO 2 2+ had the most facilitated transport observation when it reached equilibrium with the bacteria before the transport. When UO 2 2+ and bacterial were introduced to the soil at the same time or UO 2 2+ was pre-deposited in the soil, the facilitated transport was less pronounced. In the presence of phytate, bacterial-facilitated UO 2 2+ transport was hindered. pH was found to play the key role for UO 2 2+ immobilization in the presence of phytate. The immobilization of UO 2 2+ with the addition of phytate increased with the increase of pH within the pH range of this study because of the impact of pH on the solubility of UO 2 (OH) 2 . Phytate promoted UO 2 - -PO 4 3- complex and/or [Ca(UO 2 ) 2 (PO 4 ) 2 ] formation, leading to enhanced UO 2 2+ immobilization in the SRS soil., (Published by Elsevier Ltd.)

A multidisciplinary team of nurses, sterile processing technicians, and surgeons reviewed 609 otolaryngology-head and neck surgery (OHNS) surgical instrument sets at the study institution's 3 hospitals. Implementation of the 4-phase instrument review resulted in decreased OHNS surgical instrument set types from 261 to 234 sets, and a decreased number of instruments in these sets from 18 952 to 17 084. The instrument set review resulted in an estimated savings of $35 665 in sterile processing costs for the OHNS department. Instrument review applied to all 10 surgical specialties at the institution would result in an estimated annual savings of $425 378. Through effective leadership, multidisciplinary participation of all key stakeholders, and a systematic approach, this study demonstrates that a hospital-wide quality improvement intervention for instrument set optimization can be successfully performed in a large, multisite tertiary care academic hospital.

Two Burkholderia spp. (strains SRS-25 and SRS-46) were isolated from high concentrations of uranium (U) from the U.S. Department of Energy (DOE)-managed Savannah River Site (SRS). SRS contains soil gradients that remain co-contaminated by heavy metals from previous nuclear weapons production activities. Uranium (U) is one of the dominant contaminants within the SRS impacted soils, which can be microbially transformed into less toxic forms. We established microcosms containing strains SRS-25 and SRS-46 spiked with U and evaluated the microbially-mediated depletion with concomitant genomic and proteomic analysis. Both strains showed a rapid depletion of U; draft genome sequences revealed SRS-25 genome to be of approximately 8,152,324 bp, a G + C content of 66.5, containing a total 7604 coding sequences with 77 total RNA genes. Similarly, strain SRS-46 contained a genome size of 8,587,429 bp with a G + C content of 67.1, 7895 coding sequences, with 73 total RNA genes, respectively. An in-depth, genome-wide comparisons between strains 25, 46 and a previously isolated strain from our research ( Burkholderia sp. strain SRS-W-2-2016), revealed a common pool of 3128 genes; many were found to be homologues to previously characterized metal resistance genes (e.g., for cadmium, cobalt, and zinc), as well as for transporter, stress/detoxification, cytochromes, and drug resistance functions. Furthermore, proteomic analysis of strains with or without U stress, revealed the increased expression of 34 proteins from strain SRS-25 and 52 proteins from strain SRS-46; similar to the genomic analyses, many of these proteins have previously been shown to function in stress response, DNA repair, protein biosynthesis and metabolism. Overall, this comparative proteogenomics study confirms the repertoire of metabolic and stress response functions likely rendering the ecological competitiveness to the isolated strains for colonization and survival in the heavy metals contaminated SRS soil habitat.

Background: Captive cetacean attractions are growing in number globally, their operators citing entertainment, education, and conservation as benefits. Those for and against developing such attractions claim public support. Previous public opinion research, however, shows little consensus, partly due to the introduction of biases in study design that influence participants' responses. Those involved in, or concerned with, developing and licensing these attractions need to better understand what drives the lack of consensus to take socially-acceptable decisions., Methods: We reviewed previous research on public opinion of cetacean captivity, noting possible sources of bias. Survey question wording can be a major source of introduced bias, so we used an open-ended photo elicitation approach. We showed tourists in the Turks Caicos Islands ( N  = 292) images of a marine mammal park (MMP) killer whale show and a swim-with-the-dolphins (SWTD) attraction and asked for their qualitative comments on the potential development of each. They also indicated how likely they would be to visit each on a Likert scale., Results: Respondents were generally against visiting MMP killer whale shows, with 60.9% not likely to visit. SWTD attractions were more popular; 60.3% were likely to visit. For SWTD, USA residents were more likely to visit; older respondents and those staying in all-inclusive resorts were less likely. Those staying in all-inclusive resorts were also less likely to visit MMP killer whale shows. The great majority of qualitative comments centred on either entertainment value or animal welfare concerns. There were very few, if any, comments on the education or conservation value of these attractions., Discussion: Our findings contradict several previous studies on public opinion of captive cetaceans that did not use photo elicitation. The support shown for MMP killer whale shows in this survey was well below that claimed by studies conducted on behalf of captive cetacean attraction operators. Opposition to SWTD was also noticeably lower than that found in surveys conducted with wild cetacean tourism participants. This difference can likely be attributed to the different survey populations and settings, but this variation is also very likely attributable to researcher-introduced bias. While photo selection can introduce bias, photo elicitation reduces reliance on pre-scripted questions and responses, and seems to effectively reduce other forms of bias. Allowing open-ended responses, where participants responded to an image, seems to have given a more representative understanding of what is at the forefront of the public's mind than closed questioning. These conclusions, among others made in this study, suggest that development decisions for captive cetacean attractions are being made on imprecise data. Going forward, data collected via responder-led, open-ended, bias-minimising approaches should at least be considered when informing such decisions., Competing Interests: The authors declare there are no competing interests.

Purpose: To assess the clinical safety, tolerability, and efficacy of topically administered MGV354, a soluble guanylate cyclase (sGC) activator, in patients with ocular hypertension (OH) or glaucoma., Design: Double-masked, randomized, and vehicle-controlled study., Methods: Parts 1 and 2 evaluated safety and tolerability to identify the maximum tolerated dose (MTD) of once-daily MGV354 in 32 healthy volunteers (Part 1) and 16 patients with OH or glaucoma (Part 2) at a single clinical site. Part 3 was a multisite trial that evaluated intraocular pressure (IOP)-lowering efficacy of the MTD administered nightly for 1 week in 50 patients with minimum IOP of 24 mm Hg at 8 AM, with a main outcome measure of mean diurnal IOP at day 8 compared to baseline (ClinicalTrials.govNCT02743780)., Results: There was no difference in favor of MGV354 for IOP lowering; change from baseline to day 8 in mean diurnal IOP was -0.6 mm Hg for MGV354-treated patients and -1.1 mm Hg for vehicle-treated patients in Part 3, with a confidence interval of -0.7 to 1.7. The most common adverse events reported after MGV354 administration were conjunctival and ocular hyperemia., Conclusions: Overall, MGV354 0.1% demonstrated no statistically significant effect compared to vehicle in lowering IOP based on the study's main outcome measure. MGV354 produced ocular hyperemia consistent with its pharmacology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Arthrobacter sp. strain SRS-W-1-2016 was isolated on high concentrations of uranium (U) from the Savannah River Site (SRS) that remains co-contaminated by radionuclides, heavy metals, and organics. SRS is located on the northeast bank of the Savannah River (South Carolina, USA), which is a U.S. Department of Energy (DOE) managed ecosystem left historically contaminated from decades of nuclear weapons production activities. Predominant contaminants within the impacted SRS environment include U and Nickel (Ni), both of which can be transformed microbially into less toxic forms via metal complexation mechanisms. Strain SRS-W-1-2016 was isolated from the uraniferous SRS soils on high concentrations of U (4200 μM) and Ni (8500 μM), but rapid growth was observed at much lower concentrations of 500 μM U and 1000 μM Ni, respectively. Microcosm studies established with strain SRS-W-1-2016 revealed a rapid decline in the concentration of spiked U such that it was almost undetectable in the supernatant by 72 h of incubation. Conversely, Ni concentrations remained unchanged, suggesting that the strain removed U but not Ni under the tested conditions. To obtain a deeper understanding of the metabolic potential, a draft genome sequence of strain SRS-W-1-2016 was obtained at a coverage of 90×, assembling into 93 contigs with an N50 contig length of 92,788 bases. The genomic size of strain SRS-W-1-2016 was found to be 4,564,701 bases with a total number of 4327 putative genes. An in-depth, genome-wide comparison between strain SRS-W-1-2016 and its four closest taxonomic relatives revealed 1159 distinct genes, representing 26.7% of its total genome; many associating with metal resistance proteins (e.g., for cadmium, cobalt, and zinc), transporter proteins, stress proteins, cytochromes, and drug resistance functions. Additionally, several gene homologues coding for resistance to metals were identified in the strain, such as outer membrane efflux pump proteins, peptide/nickel transport substrate and ATP-binding proteins, a high-affinity nickel-transport protein, and the spoT gene, which was recently implicated in bacterial resistance towards U. Detailed genome mining analysis of strain SRS-W-1-2016 also revealed the presence of a plethora of secondary metabolite biosynthetic gene clusters likely facilitating resistance to antibiotics, biocides, and metals. Additionally, several gene homologous for the well-known oxygenase enzyme system were also identified, potentially functioning to generate energy via the breakdown of organic compounds and thus enabling the successful colonization and natural attenuation of contaminants by Arthrobacter sp. SRS-W-1-2016 at the SRS site., Competing Interests: The authors declare no conflict of interest.

Future advances in identity research will depend on integration across major theoretical traditions. Developmental-contextualism has established essential criteria to guide this effort, including specifying the context of identity development, its timing over the life course, and its content. This article assesses 4 major traditions of identity research-identity status, eudaimonic identity, sociocultural theory, and narrative identity-in light of these criteria, and describes the contribution of each tradition to the broader enterprise of developmental-contextual research. This article proposes dialectical integration of the 4 traditions, for the purpose of generating new questions when the tensions and contradictions among theoretical traditions are acknowledged. We provide examples from existing literature of the kinds of research that could address these questions and consider ways of addressing the validity issues involved in developmental-contextual identity research. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Savannah River Site (SRS), an approximately 800-km 2 former nuclear weapons production facility located near Aiken, SC remains co-contaminated by heavy metals and radionuclides. To gain a better understanding on microbially-mediated bioremediation mechanisms, several bacterial strains resistant to high concentrations of Uranium (U) and Nickel (Ni) were isolated from the Steeds Pond soils located within the SRS site. One of the isolated strains, designated as strain SRS-W-2-2016, grew robustly on both U and Ni. To fully understand the arsenal of metabolic functions possessed by this strain, a draft whole genome sequence (WGS) was obtained, assembled, annotated and analyzed. Genome-centric evaluation revealed the isolate to belong to the Burkholderia genus with close affiliation to B . xenovorans LB400, an aggressive polychlorinated biphenyl-degrader. At a coverage of 90 ×, the genome of strain SRS-W-2-2016 consisted of 8,035,584 bases with a total number of 7071 putative genes assembling into 191 contigs with an N50 contig length of 134,675 bases. Several gene homologues coding for resistance to heavy metals/radionuclides were identified in strain SRS-W-2-2016, such as a suite of outer membrane efflux pump proteins similar to nickel/cobalt transporter regulators, peptide/nickel transport substrate and ATP-binding proteins, permease proteins, and a high-affinity nickel-transport protein. Also noteworthy were two separate gene fragments in strain SRS-W-2-2016 homologous to the spoT gene; recently correlated with bacterial tolerance to U. Additionally, a plethora of oxygenase genes were also identified in the isolate, potentially involved in the breakdown of organic compounds facilitating the strain's successful colonization and survival in the SRS co-contaminated soils. The WGS project of Burkholderia sp. strain SRS-W-2-2016 is available at DDBJ/ENA/GenBank under the accession #MSDV00000000.

A challenge to all remedial approaches for contaminated sediments is the continued influx of contaminants from uncontrolled sources following remediation. We investigated the effects of ongoing contamination in mesocosms employing sediments remediated by different types of active and passive caps and in-situ treatment. Our hypothesis was that the sequestering agents used in active caps and in situ treatment will bind elements (arsenic, chromium, cadmium, cobalt, copper, nickel, lead, selenium, and zinc) from ongoing sources thereby reducing their bioavailability and protecting underlying remediated sediments from recontamination. Most element concentrations in surface water remained significantly lower in mesocosms with apatite and mixed amendment caps than in mesocosms with passive caps (sand), uncapped sediment, and spike solution throughout the 2520h experiment. Element concentrations were significantly higher in Lumbriculus variegatus from untreated sediment than in Lumbriculus from most active caps. Pearson correlations between element concentrations in Lumbriculus and metal concentrations in the top 2.5cm of sediment or cap measured by diffusive gradient in thin films (DGT) sediment probes were generally strong (as high as 0.98) and significant (p<0.05) for almost all tested elements. Metal concentrations in both Lumbriculus and sediment/cap were lowest in apatite, mixed amendment, and activated carbon treatments. These findings show that some active caps can protect remediated sediments by reducing the bioavailable pool of metals/metalloids in ongoing sources of contamination., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-κB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-κB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at  https://github.com/dib-lab/khmer/.