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Abstract Biofilm formation is an important mechanism of survival and persistence for many bacterial pathogens. These multicellular communities contain subpopulations of cells that display metabolic and transcriptional diversity along with recalcitrance to antibiotics and host immune defenses. Here, we present an optimized bacterial single-cell RNA sequencing method, BaSSSh-seq, to study Staphylococcus aureus diversity during biofilm growth and transcriptional adaptations following immune cell exposure. BaSSSh-seq captures extensive transcriptional heterogeneity during biofilm compared to planktonic growth. We quantify and visualize transcriptional regulatory networks across heterogeneous biofilm subpopulations and identify gene sets that are associated with a trajectory from planktonic to biofilm growth. BaSSSh-seq also detects alterations in biofilm metabolism, stress response, and virulence induced by distinct immune cell populations. This work facilitates the exploration of biofilm dynamics at single-cell resolution, unlocking the potential for identifying biofilm adaptations to environmental signals and immune pressure.

Abstract Background Cardiac rehabilitation has been identified as having the most homogenous clinical exercise service structure in the United Kingdom (UK), but inconsistencies are evident in staff roles and qualifications within and across services. The recognition of Clinical Exercise Physiologists (CEPs) as a registered health professional in 2021 in the UK, provides a potential solution to standardise the cardiac rehabilitation workforce. This case study examined, in a purposefully selected cardiac exercise service that employed registered CEPs, (i) how staff knowledge, skills and competencies contribute to the provision of the service, (ii) how these components assist in creating effective service teams, and (iii) the existing challenges from staff and patient perspectives. Methods A multi-method qualitative approach (inc., semi-structured interviews, observations, field notes and researcher reflections) was employed with the researcher immersed for 12-weeks within the service. The Consolidated Framework for Implementation Research was used as an overarching guide for data collection. Data derived from registered CEPs (n = 5), clinical nurse specialists (n = 2), dietitians (n = 1), service managers/leads (n = 2) and patients (n = 7) were thematically analysed. Results Registered CEPs delivered innovative exercise prescription based on their training, continued professional development (CPD), academic qualifications and involvement in research studies as part of the service. Exposure to a wide multidisciplinary team (MDT) allowed skill and competency transfer in areas such as clinical assessments. Developing an effective behaviour change strategy was challenging with delivery of lifestyle information more effective during less formal conversations compared to timetabled education sessions. Conclusions Registered CEPs have the specialist knowledge and skills to undertake and implement the latest evidence-based exercise prescription in a cardiac rehabilitation setting. An MDT service structure enables a more effective team upskilling through shared peer experiences, observations and collaborative working between healthcare professionals.

The professional identity of scientists has historically been cultivated to value research over teaching, which can undermine initiatives that aim to reform science education. Course-Based Research Experiences (CRE) and the inclusive Research and Education Communities (iREC) are two successful and impactful reform efforts that integrate research and teaching. The aim of this study is to explicate the professional identity of instructors who implement a CRE within an established iREC and to explore how this identity contributes to the success of these programs. 97 CRE instructors from the Science Education Alliance (SEA) iREC participated in a 2-year, multi-stage, qualitative research project that involved weekly reflective journaling, autoethnographic description, small group evaluation and writing, and large-scale community checking. The resulting description of professional identity consisted of shared values (inclusivity, student success, community membership, ownership/agency, science, overcoming failure, and persistence), specified roles (mentor, advocate, scientist, educator, motivator, collaborator, community builder, learner, evaluator and project manager) and a stated sense of self (dedicated, resilient, pride in students, multiskilled, valued, community member, responsible and overworked). Analysis of individual reflective diary entries revealed how a professional identity underpinned and facilitated the ways in which faculty addressed challenges that arose and worked toward the success of every student. It is the self-concept of the professional identity of the instructor in the context of the CRE classroom that directed the extended commitment and effort that these instructors evidently put into their work with students, which facilitated student engagement, student persistence, and their collective scientific output. The study concludes that a professional identity of STEM faculty in the context of a CRE and iREC combines being a researcher and educator, and that this integrated identity is central for current initiatives aimed at transforming undergraduate STEM education.

Abstract Animals can quickly adapt learned movements to external perturbations, and their existing motor repertoire likely influences their ease of adaptation. Long-term learning causes lasting changes in neural connectivity, which shapes the activity patterns that can be produced during adaptation. Here, we examined how a neural population’s existing activity patterns, acquired through de novo learning, affect subsequent adaptation by modeling motor cortical neural population dynamics with recurrent neural networks. We trained networks on different motor repertoires comprising varying numbers of movements, which they acquired following various learning experiences. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural ‘structure’—organization in the available population activity patterns. This structure facilitated adaptation, but only when the changes imposed by the perturbation were congruent with the organization of the inputs and the structure in neural activity acquired during de novo learning. These results highlight trade-offs in skill acquisition and demonstrate how different learning experiences can shape the geometrical properties of neural population activity and subsequent adaptation.

Abstract Huntington's disease (HD) is a devastating neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein, resulting from a CAG repeat expansion in the huntingtin gene HTT. HD is characterized by a variety of debilitating symptoms including involuntary movements, cognitive impairment, and psychiatric disturbances. Despite considerable efforts, effective disease-modifying treatments for HD remain elusive, necessitating exploration of novel therapeutic approaches, including lifestyle modifications that could delay symptom onset and disease progression. Recent studies suggest that time-restricted eating (TRE), a form of intermittent fasting involving daily caloric intake within a limited time window, may hold promise in the treatment of neurodegenerative diseases, including HD. TRE has been shown to improve mitochondrial function, upregulate autophagy, reduce oxidative stress, regulate the sleep–wake cycle, and enhance cognitive function. In this review, we explore the potential therapeutic role of TRE in HD, focusing on its underlying physiological mechanisms. We discuss how TRE might enhance the clearance of mHTT, recover striatal brain-derived neurotrophic factor levels, improve mitochondrial function and stress-response pathways, and synchronize circadian rhythm activity. Understanding these mechanisms is critical for the development of targeted lifestyle interventions to mitigate HD pathology and improve patient outcomes. While the potential benefits of TRE in HD animal models are encouraging, future comprehensive clinical trials will be necessary to evaluate its safety, feasibility, and efficacy in persons with HD.

Abstract Background There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. Results In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. Conclusions This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.

Background: Total hip arthroplasty (THA) was removed from the Centers for Medicare and Medicaid Services inpatient-only (IPO) list on January 1, 2020. The impact of this policy changes on length of stay (LOS) and coding status (inpatient/outpatient) beyond 2020 remains to be fully defined. Methods: Data were obtained from the 2018 to 2021 National Surgical Quality Improvement Program database. Elective primary THA patients aged 18 y or older were identified by Current Procedural Terminology code. Year of surgery, age (dichotomized at ≥/

Fungal toxins in local food supplies are a critical environmental health risk to communities globally. To better characterize hypothesized toxin control points among households, we conducted household surveys across four departments (first administrative division) in Guatemala. Data gathered included maize harvesting, processing, storage, and traditional nixtamalization practices. In total, n = 33 households participated in the survey and were from 4 unique departments, 17 unique municipalities, and represented 4 different languages. The results suggested that the majority of households consumed a combination of personally cultivated and purchased maize. There was significant variation in how this maize was stored, in regards to pre-processing (kernel vs whole cob), as well as storage system type. For nixtamalization, the largest differences in practices (e.g., cooking time) were based on household size while the majority of households reported practices that aligned with previously reported best practices. Lastly, all reported maize-based food products produced by households utilized the nixtamalization process except one. Current maize handling and nixtamalization practices reported by a majority of households aligned with best practices, however, with locally tailored and culturally sensitive guidance disseminated by key stakeholders, the prevalence of best practice use among households can be improved. Further community-based research on traditional farming and nixtamalization practices can improve these recommendations.

Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

Background: Nerve injury following total hip arthroplasty (THA) is a rare but serious adverse event. While prior studies have reported risk factors for nerve injury related to THA, they are limited to institutional data or small sample sizes. The current study aimed to leverage a large, national database to assess independent risk factors for sustaining nerve injury with THA. Methods: The 2010-2021 PearlDiver M157 database was queried for adult THA cases. Those with nerve injury within 90 days of THA were identified. Patient age, sex, body mass index (BMI), Elixhauser comorbidity index (ECI), fracture indication, and surgery type (index vs revision) were assessed for correlation with nerve injury by multivariate analyses. Results: Out of 750,695 THAs, 2659 (0.35%) had nerve injuries. Multivariate analysis revealed independent predictors of nerve injury in decreasing odds ratio (OR) order to include: revision procedure (OR: 2.13), female sex (OR 1.35), ECI (ECI 1-2 [OR 1.27], ECI 3-4 [OR 1.43], and ECI ≥5 [OR 1.59]) and age (OR 1.02 per decade decrease) (P < .05 for each). Pertinent negatives by multivariate analysis included underweight BMI (

Animals exhibit dynamic movement and activity in response to environmental variation including changes in reproductive opportunities, predation risk, or food availability. Yet, it remains unclear which factors are primary in affecting animal movement, and whether the relative importance of these factors are consistent through time. We tracked snowshoe hares (Lepus americanus) using GPS telemetry during eight summers spanning a hare population cycle (2015–2022) in southwestern Yukon, Canada, to determine associations between environmental variation and hare movement and home range size. Hare density varied 25-fold during the study and home range size increased markedly during low hare density, especially for males. Both sexes retained similar core space use and linearity of movements, but at low densities males had greater and more variable movement rates and time spent travelling. Trail cameras revealed that annual changes in hare movement were also correlated with relative abundance of lynx (Lynx canadensis) and coyotes (Canis latrans). However, hare detection rates within a season were not closely associated with seasonal variation in predator detection. Observed differences between male and female hares in some metrics highlighted that different life histories and reproductive behavior are likely the main drivers of hare movement dynamics. Therefore, fitness rewards associated with successful mate search and reproduction appear to outweigh risks associated with increased movement, even in highly variable environments where costs of prioritizing reproduction-related activities are notably high and variable.

Trees that survive disturbances are important biological legacies that facilitate forests’ recovery and enhance their structural and species diversity, substantially contributing to the resilience of these ecosystems. The dynamic pattern of legacy syndromes sets the understudied aspects of survivors of wind disturbance into focus. Several factors at tree, stand, and landscape scales alter the susceptibility of the remnant trees, and affect their potential to recover and survive subsequent disturbances. The characteristics of the survivors interact with direct stress and mortality drivers such as changed environmental conditions and pressure by pests and pathogens. Climate change further enhances the post-storm vulnerability of the remaining stand. This literature review analyzes the impact of disturbance parameters (e.g., severity, seasonal timing) and characteristics of the affected forest (e.g., tree species composition, successional stage of a forest stand) on the conditions of survivors through post-windthrow stand development. We attempted to reveal the main agents and processes driving the fate of remnant trees and linked delayed mortality patterns to the main stand-scale wind disturbance regimes in Eurasian and North American boreal and temperate forests: (1) stand-replacing, (2) partially stand-replacing, and (3) fine-scale gap disturbance. We found that after stand-replacing wind disturbance, the spatial location of the remaining trees largely determines their onward fate, whereas these survivors are generally more susceptible to subsequent mortality compared to trees that survived less severe events. After partially stand-replacing wind disturbance, the structure of the remnant stand as well as characteristics of the individual remnant trees (e.g., species, age, size) largely determine their survival probability. Following a fine-scale gap disturbance, the trees at the gap edge are more likely to die, compared to the trees situated in the stand interior, but the mortality-causing processes usually operate on a longer time scale. Our findings contribute to the current knowledge on post-windthrow stand development and offer insights into temporal stability of these increasingly important biological legacies.

Fire is a highly important factor affecting the forest structure as well as its functions. The understanding of the post-fire recovery mechanisms could be especially useful in the face of globally increasing fire frequencies. Fire-adapted forests in Minnesota provide a unique opportunity to study these recovery mechanisms due to their long and well-documented history of prescribed burnings and wildfires. We investigated oribatid mite (Acari: Oribatida) assemblages along a 126-year post-fire chronosequence, together with soil physical, chemical and microbial properties (e.g. bulk density, organic matter content, C, N and P content, microbial biomass). Whereas the effect of prescribed burning was negligible, the wildfire decreased oribatid density (–86 %) and diversity (–38 %) for at least 13 years. The recovery of oribatid mites corresponded to the changes in soil properties, being correlated negatively to bulk density and positively to organic matter content, water holding capacity and microbial activity and biomass. The recovery did not depend simply on the time elapsed since fire, but it was rather a complex response to long-term (15–20 years), fire-induced changes in the soil environment.

Abstract Background Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated with CTE pathology are unclear. In brain donors with autopsy-confirmed CTE, we investigated the association of CTE p-tau pathology density and location with cognitive, functional, and neuropsychiatric symptoms. Methods In 364 brain donors with autopsy confirmed CTE, semi-quantitative p-tau severity (range: 0–3) was assessed in 10 cortical and subcortical regions. We summed ratings across regions to form a p-tau severity global composite (range: 0–30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF-A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF-A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS-11), aggression (Brown-Goodwin Aggression Scale), depression (Geriatric Depression Scale-15, GDS-15), and apathy (Apathy Evaluation Scale, AES). Ordinary least squares regression models examined associations between global and regional p-tau severity (separate models for each region) with each clinical scale, adjusting for age at death, racial identity, education level, and history of hypertension, obstructive sleep apnea, and substance use treatment. Ridge regression models that incorporated p-tau severity across all regions in the same model assessed which regions showed independent effects. Results The sample was predominantly American football players (333; 91.2%); 140 (38.5%) had low CTE and 224 (61.5%) had high CTE. Global p-tau severity was associated with higher (i.e., worse) scores on the cognitive and functional scales: MI ( $$\beta$$ β standardized = 0.02, 95%CI = 0.01–0.04), CDS ( $$\beta$$ β standardized = 0.02, 95%CI = 0.01–0.04), and FAQ ( $$\beta$$ β standardized = 0.03, 95%CI = 0.01–0.04). After false-discovery rate correction, p-tau severity in the frontal, inferior parietal, and superior temporal cortex, and the amygdala was associated with higher CDS ( $$\beta$$ β sstandardized = 0.17–0.29, ps

Abstract A previous study on the encroachment of North American northern red oak Quercus rubra L. into the mesic Scots pine forest (in central Poland) revealed high abundances of seedlings and saplings under shrubs, with lower abundances in open areas or clumps of bilberry Vaccinium myrtillus L. It was unclear whether the regeneration success of Q. rubra is enhanced by the presence of shrubs due to their “nurse effect”, and how burying acorns of different sizes in soil or moss affects the survival of oak seeds and seedlings (a “burial effect”). Results of a previous observational study were verified in an experimental study: a pool of 900 large‐, medium‐, and small‐sized acorns was sown under moss cover in open areas and within bilberry clumps and in soil under shrubs in 2018 and monitored for 3 years in natural conditions. The majority of sown acorns were lost, mainly due to acorn pilferage, lack of germination and the death of sprouting acorns. However, acorn and seedling survival depended significantly on acorn size and differed among the microsites studied. Viable seedlings were twice as likely to develop from large‐ and medium‐sized as from small‐sized acorns, and they grew mainly from acorns sown under moss cover, confirming a positive “burial effect.” Seedling survival was three times higher in bilberry and open areas, than under shrubs; however, seedlings “nursed” by shrubs were less threatened by large ungulates. Only a small part of the pool of sown acorns contributes to the reproductive success of Q. rubra in the mesic Scots pine forest. Microsites characteristic to this type of forest are suitable for northern red oak regeneration; however, bilberry favors acorn survival and germination and early seedling growth, moss cover favors acorn survival and germination, while shrubs protect surviving seedlings from herbivory.

Abstract The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded – in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands – the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger’s movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation.

Abstract Electrical stimulation of the neuromuscular system holds promise for both scientific and therapeutic biomedical applications. Supplying and maintaining the power necessary to drive stimulation chronically is a fundamental challenge in these applications, especially when high voltages or currents are required. Wireless systems, in which energy is supplied through near field power transfer, could eliminate complications caused by battery packs or external connections, but currently do not provide the harvested power and voltages required for applications such as muscle stimulation. Here, we introduce a passive resonator optimized power transfer design that overcomes these limitations, enabling voltage compliances of ± 20 V and power over 300 mW at device volumes of 0.2 cm2, thereby improving power transfer 500% over previous systems. We show that this improved performance enables multichannel, biphasic, current-controlled operation at clinically relevant voltage and current ranges with digital control and telemetry in freely behaving animals. Preliminary chronic results indicate that implanted devices remain operational over 6 weeks in both intact and spinal cord injured rats and are capable of producing fine control of spinal and muscle stimulation.

Food crops around the world are commonly contaminated with Aspergillus flavus, which can produce the carcinogenic mycotoxin aflatoxin B1 (AFB1). The objective of this study is to test an X-ray irradiation sterilization method for studying AFB1 in contaminated maize samples in the laboratory. Maize that had been naturally contaminated with 300 ppb AFB1 by the growth of aflatoxigenic A. flavus was ground and then irradiated at 0.0, 1.0, 1.5, 2.0, 2.5, and 3.0 kGy. A. flavus was quantified by dilution plating on potato dextrose agar (PDA) and modified Rose Bengal media (MDRB) for viability and qPCR for gene presence. AFB1 was quantified by HPLC and ELISA. A. flavus viability, but not gene copies, significantly decreased with increasing doses of radiation (PDA: p < 0.001; MDRB: p < 0.001; qPCR: p = 0.026). AFB1 concentration did not significantly change with increasing doses of radiation (HPLC: p = 0.153; ELISA: p = 0.567). Our results imply that X-ray irradiation is an effective means of reducing viable A. flavus without affecting AFB1 concentrations. Reducing the hazard of fungal spores and halting AFB1 production at the targeted dose are important steps to safely and reproducibly move forward research on the global mycotoxin challenge.

Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI), but the components of RHI exposure underlying this relationship are unclear. We create a position exposure matrix (PEM), composed of American football helmet sensor data, summarized from literature review by player position and level of play. Using this PEM, we estimate measures of lifetime RHI exposure for a separate cohort of 631 football playing brain donors. Separate models examine the relationship between CTE pathology and players’ concussion count, athletic positions, years of football, and PEM-derived measures, including estimated cumulative head impacts, linear accelerations, and rotational accelerations. Only duration of play and PEM-derived measures are significantly associated with CTE pathology. Models incorporating cumulative linear or rotational acceleration have better model fit and are better predictors of CTE pathology than duration of play or cumulative head impacts alone. These findings implicate cumulative head impact intensity in CTE pathogenesis.

Introduction: The research criteria for prodromal Parkinson disease (pPD) depends on prospectively validated clinical inputs with large effect sizes and/or high prevalence. Neither traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), nor chronic pain are currently included in the calculator, despite recent evidence of association with pPD. These conditions are widely prevalent, co-occurring, and already known to confer risk of REM behavior disorder (RBD) and PD. Few studies have examined PD risk in the context of TBI and PTSD; none have examined chronic pain. This study aimed to measure the risk of pPD caused by TBI, PTSD, and chronic pain. Methods: 216 US Veterans were enrolled who had self-reported recurrent or persistent pain for at least three months. Of these, 44 met criteria for PTSD, 39 for TBI, and 41 for all three conditions. Several pain, sleep, affective, and trauma questionnaires were administered. Participants’ history of RBD was determined via self-report, with a subset undergoing confirmatory video polysomnography. Results: A greater proportion of Veterans with chronic pain met criteria for RBD (36 % vs. 10 %) and pPD (18.0 % vs. 8.3 %) compared to controls. Proportions were increased in RBD (70 %) and pPD (27 %) when chronic pain co-occurred with TBI and PTSD. Partial effects were seen with just TBI or PTSD alone. When analyzed as continuous variables, polytrauma symptom severity correlated with pPD probability (r = 0.28, P = 0.03). Conclusion: These data demonstrate the potential utility of chronic pain, TBI, and PTSD in the prediction of pPD, and the importance of trauma-related factors in the pathogenesis of PD.

Abstract Background In accordance with guidelines, observation with or without active surveillance for low‐risk prostate cancer increased in recent years in the general population. We compared treatment patterns and mortality for low‐ and intermediate‐risk prostate cancer and mortality rates among end‐stage kidney disease (ESKD) and non‐ESKD patients. Methods This is a retrospective population‐based observational cohort study of Surveillance, Epidemiology, and End Results‐Medicare data of men aged 66 years and older with localized prostate cancer (2004–2015). ESKD status was determined using Medicare billing codes. Multivariable logistic regression models and Cox‐proportional hazards models were used to study definitive treatment patterns and mortality, respectively. Results For low‐risk prostate cancer, dialysis patients (N = 83) had lower but not statistically significant odds (OR, 0.74; 95% CI: 0.48–1.16) of receiving definitive treatment than non‐ESKD patients (N = 24,935). For those with intermediate‐risk prostate cancer, dialysis patients (N = 254) had lower odds to receive definitive treatment (OR, 0.54; 95% CI: 0.42–0.72) than non‐ESKD patients (N = 60,883). From 2004–2010 to 2011–2015, for patients with low‐risk prostate cancer, while the receipt of definitive treatment for non‐ESKD patients trended down from 72% to 48%, it trended up for dialysis patients from 55% to 65%. Kidney transplant patients (N = 33 for low‐risk and N = 91 for intermediate‐risk) had lower rates of definitive treatment for low‐risk and similar rates of treatment for intermediate‐risk prostate cancer compared to non‐ESKD patients. Conclusions The disparity in definitive treatment rates for low‐risk prostate cancer among dialysis patients exists despite their high mortality, compared to the general population.

Protrusio acetabuli is a unique osteological condition that has been long described in the literature and is known to potentially increase both the surgical complexity and the risk of complications when performing total hip arthroplasty. Although grading systems for native hip protrusio have been described in the past, there has not yet been a widely adopted classification system that categorizes the condition into separate classes in order to guide management. We propose a novel classification system with the goal of simplifying and standardizing the management of protrusio acetabuli in the context of modern total hip arthroplasty. This classification system describes protrusio based on the relationship of the femoral head to the ilioischial and iliopectineal lines, allowing for a more reproducible and consistent categorization of pathology. We also discuss general recommendations and technical pearls for total hip arthroplasty in the protrusio patient population, including the use of strategic soft tissue releases, fluoroscopy, navigation, bone graft, and augments.

Abstract Background Over the last decade use of raw acceleration metrics to assess physical activity has increased. Metrics such as Euclidean Norm Minus One (ENMO), and Mean Amplitude Deviation (MAD) can be used to generate metrics which describe physical activity volume (average acceleration), intensity distribution (intensity gradient), and intensity of the most active periods (MX metrics) of the day. Presently, relatively little comparative data for these metrics exists in youth. To address this need, this study presents age- and sex-specific reference percentile values in England youth and compares physical activity volume and intensity profiles by age and sex. Methods Wrist-worn accelerometer data from 10 studies involving youth aged 5 to 15 y were pooled. Weekday and weekend waking hours were first calculated for youth in school Years (Y) 1&2, Y4&5, Y6&7, and Y8&9 to determine waking hours durations by age-groups and day types. A valid waking hours day was defined as accelerometer wear for ≥ 600 min·d−1 and participants with ≥ 3 valid weekdays and ≥ 1 valid weekend day were included. Mean ENMO- and MAD-generated average acceleration, intensity gradient, and MX metrics were calculated and summarised as weighted week averages. Sex-specific smoothed percentile curves were generated for each metric using Generalized Additive Models for Location Scale and Shape. Linear mixed models examined age and sex differences. Results The analytical sample included 1250 participants. Physical activity peaked between ages 6.5–10.5 y, depending on metric. For all metrics the highest activity levels occurred in less active participants (3rd-50th percentile) and girls, 0.5 to 1.5 y earlier than more active peers, and boys, respectively. Irrespective of metric, boys were more active than girls (p

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education.

Abstract Introduction This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p‐tau)181+231. Methods Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross‐sectional and longitudinal outcomes. Results Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia. Discussion Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.

Abstract Background Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35–52% of patients and accounting for 20–40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD. Methods A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from − 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤ − 2.5 or ≥ + 2.5 with a standard deviation not crossing zero. Results Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants. Conclusions This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.

Among island communities, water security and access continue to be a critical issue. In the US Virgin Islands (USVI), 90% of households are capable of collecting roof-harvested rainwater, whereas less than 25% of households are connected to a municipal water system serviced by desalination plants. Rainwater collection leaves the household in charge of managing and treating their own water. Therefore, understanding current barriers to accessing water treatment technologies and the costs of a water storage and treatment program at scale are critical in developing a territory-wide program. In this study, we evaluate (1) household-level barriers to accessing water treatment technologies, (2) a cost breakdown of a UV water treatment pilot program, and (3) potential estimates of program costs at a territory-wide scale. The results suggest that for households, key barriers include knowledge of the problem or solution and capital and installation costs. From the programmatic cost evaluation, the water treatment technology and water testing services were the most expensive. However, given key adjustments, a territory-wide program is estimated to cost $30.4 M covering 50% of households. These data can be used by a coalition of stakeholders in allocating financial and managerial responsibility for a territory-wide water storage and treatment program in USVI. HIGHLIGHTS Households in USVI are responsible for treating and storing their water supply.; The primary barriers to acquiring adequate treatment are knowledge of the problem and capital costs of the technology.; A water treatment pilot program identified the highest cost components as the treatment technology and water testing.; A territory-wide water treatment program is estimated to cost $30.4 M to cover 50% of the population.;

Abstract Modern myoelectric prosthetic hands have multiple independently controllable degrees of freedom, but require constant visual attention to use effectively. Somatosensory feedback provides information not available through vision alone and is essential for fine motor control of our limbs. Similarly, stimulation of the nervous system can potentially provide artificial somatosensory feedback to reduce the reliance on visual cues to efficiently operate prosthetic devices. We have shown previously that epidural stimulation of the lateral cervical spinal cord can evoke tactile sensations perceived as emanating from the missing arm and hand in people with upper-limb amputation. In this case study, two subjects with upper-limb amputation used this somatotopically-matched tactile feedback to discriminate object size and compliance while controlling a prosthetic hand. With less than 30 min of practice each day, both subjects were able to use artificial somatosensory feedback to perform a subset of the discrimination tasks at a success level well above chance. Subject 1 was consistently more adept at determining object size (74% accuracy; chance: 33%) while Subject 2 achieved a higher accuracy level in determining object compliance (60% accuracy; chance 33%). In each subject, discrimination of the other object property was only slightly above or at chance level suggesting that the task design and stimulation encoding scheme are important determinants of which object property could be reliably identified. Our observations suggest that changes in the intensity of artificial somatosensory feedback provided via spinal cord stimulation can be readily used to infer information about object properties with minimal training.

How animals are able to rapidly adapt their behaviour to changing environmental demands remains poorly understood. Here, the authors use a modelling approach to show that synaptic plasticity in motor cortex may underlie rapid motor learning, demonstrating that small, correlated connectivity changes that preserve neural covariance are highly effective in driving behavioural adaptation.

Background: Until recently, the properties of microbiome and mycobiome in humans and its relevance to disease have largely been unexplored. While the interest of microbiome and malignancy over the past few years have burgeoned with advent of new technologies, no research describing the composition of mycobiome in bladder cancer has been done. Deciphering of the metagenome and its aggregate genetic information can be used to understand the functional properties and relationships between the bacteria, fungi, and cancer. Objective: The aim of this project is to characterize the compositional range of the normal versus bladder cancer mycobiome of the gut. Design, setting, and participants: An internal transcribed spacer (ITS) survey of 52 fecal samples was performed to evaluate the gut mycobiome differences between noncancer controls and bladder cancer patients. Outcome measurements and statistical analysis: Our study evaluated the differences in mycobiome among patients with bladder cancer, versus matched controls. Our secondary analysis evaluated compositional differences in the gut as a function of response status with neoadjuvant chemotherapy. Data demultiplexing and classification were performed using the QIIME v.1.1.1.1 platform. The Ion Torrent–generated fungal ITS sequence data were processed using QIIME (v.1.9.1), and the reads were demultiplexed, quality filtered, and clustered into operation taxonomic units using default parameters. Alpha and beta diversity were computed and plotted in Phyloseq, principal coordinate analysis was performed on Bray-Curtis dissimilarity indices, and a one-way permutational multivariate analysis of variance was used to test for significant differences between cohorts. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition. Results and limitations: We found distinctive mycobiome differences between control group (n = 32) and bladder cancer (n = 29) gut flora, and identified an increasing abundance of Tremellales, Hypocreales, and Dothideales. Significant differences in alpha and beta diversity were present between the groups (control vs bladder; p = 0.002), noting distinct compositions within each cohort. A subgroup analysis by sex and neoadjuvant chemotherapy status did not show any further differences in mycobiome composition and diversity. Our results indicate that the gut mycobiome may modulate tumor response to preoperative chemotherapy in bladder cancer patients. We propose that patients with a “favorable” mycobiome composition (eg, high diversity, and low abundance of Agaricomycetes and Saccharomycetes) may have enhanced systemic immune response to chemotherapy through antigen presentation. Conclusions: Our study is the first to characterize the enteric mycobiome in patients with bladder cancer and describe complex ecological network alterations, indicating complex bacteria-fungi interactions, particularly highlighted among patients with complete neoadjuvant chemotherapy response. Patient summary: Our study has demonstrated that the composition of stool mycobiome (fungal inhabitants of the gastrointestinal tract) in patients with bladder cancer is different from that in noncancer individuals. Furthermore, when evaluating how patients respond to chemotherapy given prior to their surgery, our study noted significant differences between patients who responded and those who did not.

Advancements in molecular and phylogenetic analysis have revealed the need for greater taxonomic resolution since Rangifer (Reindeer and caribou: Cervidae) was last revised in 1961. Recent literature shows that many of the subspecies and several species synonymised out of existence are, in fact, valid, some names have been misapplied, and new subspecies-level clades are in need of description. This paper reviews available names for recently defined ecotypes of reindeer and caribou in compliance with ICZN rules for zoological nomenclature.

Background: Unicompartmental knee arthroplasty (UKA) may be considered for select patients to relieve pain and restore function of the knee joint. Little research to date has explored the complication profile of UKA in an older population. The current study uses a large national surgical database to examine the 30-day postoperative adverse events in octogenarians compared with those in nonoctogenarians. Material and methods: The 2012-2018 National Surgical Quality Improvement Program database was queried for all patients undergoing UKA for osteoarthritis. Those patients aged 80 years or older composed the octogenarian age group. Demographics and medical comorbidities were cataloged, in addition to 30-day adverse events. Multivariate regression analysis controlled for differences in demographics and comorbidities. Significance was set at P < .05. Results: A total of 10,103 patients undergoing UKA were identified, of which 728 (7.2%) were octogenarians. The octogenarian cohort had significantly higher comorbidity burden than nonoctogenarians. After controlling for demographics other than age, American Society of Anesthesiologists score, and medical comorbidities, octogenarians had higher 30-day odds of death (odds ratio [OR] = 6.12, P = .024), minor adverse events (OR = 2.97, P = .001), prolonged hospital length of stay (OR = 2.30,

Abstract Exposure to military blast and repetitive head impacts (RHI) in contact sports is associated with increased risk of long-term neurobehavioral sequelae and cognitive deficits, and the neurodegenerative disease chronic traumatic encephalopathy (CTE). At present, the exact pathogenic mechanisms of RHI and CTE are unknown, and no targeted therapies are available. Astrocytes have recently emerged as key mediators of the multicellular response to head trauma. Here, we investigated interface astrogliosis in blast and impact neurotrauma, specifically in the context of RHI and early stage CTE. We compared postmortem brain tissue from former military veterans with a history of blast exposure with and without a neuropathological diagnosis of CTE, former American football players with a history of RHI with and without a neuropathological diagnosis of CTE, and control donors without a history of blast, RHI exposure or CTE diagnosis. Using quantitative immunofluorescence, we found that astrogliosis was higher at the grey-white matter interface in the dorsolateral frontal cortex, with mixed effects at the subpial surface and underlying cortex, in both blast and RHI donors with and without CTE, compared to controls. These results indicate that certain astrocytic alterations are associated with both impact and blast neurotrauma, and that different astroglial responses take place in distinct brain regions.

Background: Public interest in alternative, nonoperative treatments for the management of arthritis has increased. Few have been approved by the Food and Drug Administration. The present study aimed to evaluate trends in public and scientific interest in 4 such treatments by assessing Google Trends and publication frequency data, respectively. Material and methods: Turmeric, stem cell therapy, platelet-rich plasma (PRP) therapy, and cannabidiol (CBD) were studied. For 2010-2019, Google Trends data and publication frequency data on PubMed were collected by year for arthritis and each of the 4 therapies. Linear, quadratic, and exponential regressions were applied, and the best model of growth was identified. Results: From 2010 to 2019, Google Trends annual scores for arthritis and turmeric (exponential; R2: 90.5%, P < .001), CBD (exponential; R2: 99.3%, P < .001), stem cell therapy (exponential; R2: 86.7%, P

Abstract Background Cerebrospinal fluid (CSF) tau and beta-amyloid levels in chronic traumatic encephalopathy (CTE), a disease which can be clinically indistinguishable from Alzheimer’s disease (AD), are largely unknown. We examined postmortem CSF analytes among participants with autopsy confirmed CTE and AD. Methods In this cross-sectional study 192 participants from the Boston University AD Research Center, VA-BU-CLF Center, and Framingham Heart Study (FHS) had post-mortem CSF collected at autopsy. Participants were divided into pathological groups based on AD and CTE criteria, with 61 CTE participants (18 low, 43 high stage), 79 AD participants (23 low, 56 intermediate to high), 11 participants with CTE combined with AD, and 41 participants lacking both CTE and AD neuropathology. The Meso Scale Discovery immunoassay system was utilized to measure amyloid-beta (Aβ1-40, Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau181 and p-tau231). CSF analytes were then compared across the pathological groups: no CTE/no AD (control), Low CTE, Low AD, High CTE, Intermediate/High AD, and AD+CTE. Results Among the Low disease state groups, the Low CTE group had significantly higher levels of p-tau231 versus the control group and compared to the Low AD group. The Low CTE group was also found to have significantly lower levels of Aβ1-42 compared to the control group. The high CTE group had higher levels of p-tau231 and lower levels of Aβ1-42 compared to Intermediate/High AD group. Conclusions Importantly, p-tau231 and Aβ1-42 were predictors of diagnosis of CTE vs. control and CTE vs. AD. Increased CSF p-tau231 is a promising potentially sensitive biomarker of CTE, and CSF Aβ1-42 needs further investigation in CTE.

Background: Intracortical microstimulation (ICMS) is used to map neural circuits and restore lost sensory modalities such as vision, hearing, and somatosensation. The spatial effects of ICMS remain controversial: Stoney and colleagues proposed that the volume of somatic activation increased with stimulation intensity, while Histed et al., suggested activation density, but not somatic activation volume, increases with stimulation intensity. Objective: We used computational modeling to quantify the spatial effects of ICMS intensity and unify the apparently paradoxical findings of Histed and Stoney. Methods: We implemented a biophysically-based computational model of a cortical column comprising neurons with realistic morphology and representative synapses. We quantified the spatial effects of single pulses and short trains of ICMS, including the volume of activated neurons and the density of activated neurons as a function of stimulation intensity. Results: At all amplitudes, the dominant mode of somatic activation was by antidromic propagation to the soma following axonal activation, rather than via transsynaptic activation. There were no occurrences of direct activation of somata or dendrites. The volume over which antidromic action potentials were initiated grew with stimulation amplitude, while the volume of somatic activation increased marginally. However, the density of somatic activation within the activated volume increased with stimulation amplitude. Conclusions: The results resolve the apparent paradox between Stoney and Histed's results by demonstrating that the volume over which action potentials are initiated grows with ICMS amplitude, consistent with Stoney. However, the volume occupied by the activated somata remains approximately constant, while the density of activated neurons within that volume increase, consistent with Histed.

Background: Studies analyzing the incidence and clinical implications of postoperative hematomas after total hip arthroplasty (THA) remain limited. The purpose of the present study was to use the National Surgical Quality Improvement Program (NSQIP) dataset to determine rates, risk factors, and subsequent complications of postoperative hematomas requiring reoperation after primary THA. Methods: Study population included patients who underwent primary THA (CPT code: 27130) from 2012-2016 recorded in NSQIP. Patients who developed a hematoma requiring reoperation in the 30-day postoperative period were identified. Multivariate regressions were created to identify patient characteristics, operative variables, and subsequent complications that were associated with a postoperative hematoma requiring reoperation. Results: Among the 149,026 patients who underwent primary THA, 180 (0.12%) developed a postoperative hematoma requiring reoperation. Risk factors included body mass index (BMI) ≥ 35 (relative risk [RR]: 1.83, P = .011), American Society of Anesthesiologists (ASA) class ≥3 (RR: 2.11, P < .001), and history of bleeding disorder (RR: 2.71, P < .001). Associated intraoperative characteristics were an operative time ≥100 minutes (RR: 2.03, P < .001) and use of general anesthesia (RR: 1.41, P = .028). Patients developing a hematoma requiring reoperation were at higher risk of subsequent deep wound infection (RR: 21.57, P < .001), sepsis (RR: 4.3, P = .012), and pneumonia (RR: 3.69, P = .023). Conclusions: Surgical evacuation for a postoperative hematoma was performed in about 1 in 833 cases of primary THA. Several nonmodifiable and modifiable risk factors were identified. Given the 21.6 times increased risk of subsequent deep wound infection, select, at-risk patients may benefit from closer monitoring for signs of infection.

The morphological traits of seeds have a fundamental meaning for spread and regeneration of non-native zoochorous plants, as they determine the level of establishment success and the ability of native fauna to disperse the alien plant. Here we studied the size, mass and viability of acorns of the North-American northern red oak Quercus rubra in its introduced range (in central Poland). The study revealed that acorns sampled in 2018 and 2019, in Q. rubra stands which had just reached sexual maturity, achieved optimum age for seed crop production, or were close to the rotation age, and were planted in sites suitable to European coniferous, mixed, and deciduous forests, differed in their dimensions and weight. Acorn size, mass and viability were affected both by stand age and forest site type, but more strongly by the first factor, i.e. the older the stand, the larger the acorns. At the initial stage of reproduction larger acorns were produced in coniferous than in other forest sites, but this advantage decreased with the age of stand in favour of more fertile mixed and deciduous forest sites. Acorn dimensions and viability also differed in sequential years: larger acorns with a high proportion of viability were produced in 2018, while in 2019 the proportion of viable acorns was significantly lower. The moisture of (viable) acorns was well above the lethal level for most acorns in all stands studied, however, it was impacted by the autumn weather.The high intraspecific variability in size and weight makes Q. rubra acorns attractive for different species of native seed hoarders. It conditions effective acorn spread and regeneration of this introduced (invasive) oak in European forests. Therefore, leaving single oak trees over 90 years old – which produce the best quality seeds – on plots cleared during forestry operations can favour Q. rubra regeneration.

While conventional magnetic resonance imaging (MRI) is central to the evaluation of patients with multiple sclerosis, its role in detecting the pathophysiology underlying neurodegeneration is more limited. One of the common outcome measures for progressive multiple sclerosis trials, atrophy on brain MRI, is non-specific and reflects end-stage changes after considerable neurodegeneration has occurred. Identifying biomarkers that identify processes underlying neurodegeneration before it is irreversible and that reflect relevant neurodegenerative pathophysiology is an area of significant need. Accumulating evidence suggests that oxidative stress plays a major role in the pathogenesis of multiple neurodegenerative diseases, including multiple sclerosis. Imaging markers related to inflammation, myelination, and neuronal integrity have been areas of advancement in recent years but oxidative stress has remained an area of unrealized potential. In this article we will begin by reviewing the role of oxidative stress in the pathogenesis of multiple sclerosis. Chronic inflammation appears to be directly related to the increased production of reactive oxygen species and the effects of subsequent oxidative stress appear to be amplified by aging and accumulating disease. We will then discuss techniques in development used in the assessment of MS as well as other models of neurodegenerative disease in which oxidative stress is implicated. Multiple blood and CSF markers of oxidative stress have been evaluated in subjects with MS, but non-invasive imaging offers major upside in that it provides real-time assessment within the brain.

A campaign is underway to clear established forests and expand early-successional habitats—also called young forest, pre-forest, early seral, or open habitats—with the intention of benefitting specific species. Coordinated by federal and state wildlife agencies, and funded with public money, public land managers work closely with hunting and forestry interests, conservation organizations, land trusts, and private landowners toward this goal. While forest-clearing has become a major focus in the Northeast and Upper Great Lakes regions of the U.S., far less attention is given to protecting and recovering old-forest ecosystems, the dominant land cover in these regions before European settlement. Herein we provide a discussion of early-successional habitat programs and policies in terms of their origins, in the context of historical baselines, with respect to species’ ranges and abundance, and as they relate to carbon accumulation and ecosystem integrity. Taken together, and in the face of urgent global crises in climate, biodiversity, and human health, we conclude that public land forest and wildlife management programs must be reevaluated to balance the prioritization and funding of early-successional habitat with strong and lasting protection for old-growth and mature forests, and, going forward, must ensure far more robust, unbiased, and ongoing monitoring and evaluation.

Abstract Background Chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, cannot currently be diagnosed during life. Atrophy patterns on magnetic resonance imaging could be an effective in vivo biomarker of CTE, but have not been characterized. Mechanisms of neurodegeneration in CTE are unknown. Here, we characterized macrostructural magnetic resonance imaging features of brain donors with autopsy-confirmed CTE. The association between hyperphosphorylated tau (p-tau) and atrophy on magnetic resonance imaging was examined. Methods Magnetic resonance imaging scans were obtained by medical record requests for 55 deceased symptomatic men with autopsy-confirmed CTE and 31 men (n = 11 deceased) with normal cognition at the time of the scan, all >60 years Three neuroradiologists visually rated regional atrophy and microvascular disease (0 [none]–4 [severe]), microbleeds, and cavum septum pellucidum presence. Neuropathologists rated tau severity and atrophy at autopsy using semi-quantitative scales. Results Compared to unimpaired males, donors with CTE (45/55=stage III/IV) had greater atrophy of the orbital-frontal (mean diff.=1.29), dorsolateral frontal (mean diff.=1.31), superior frontal (mean diff.=1.05), anterior temporal (mean diff.=1.57), and medial temporal lobes (mean diff.=1.60), and larger lateral (mean diff.=1.72) and third (mean diff.=0.80) ventricles, controlling for age at scan (ps

Abstract Himalayan glaciers are undergoing rapid mass loss but rates of contemporary change lack long-term (centennial-scale) context. Here, we reconstruct the extent and surfaces of 14,798 Himalayan glaciers during the Little Ice Age (LIA), 400 to 700 years ago. We show that they have lost at least 40 % of their LIA area and between 390 and 586 km3 of ice; 0.92 to 1.38 mm Sea Level Equivalent. The long-term rate of ice mass loss since the LIA has been between − 0.011 and − 0.020 m w.e./year, which is an order of magnitude lower than contemporary rates reported in the literature. Rates of mass loss depend on monsoon influence and orographic effects, with the fastest losses measured in East Nepal and in Bhutan north of the main divide. Locally, rates of loss were enhanced with the presence of surface debris cover (by 2 times vs clean-ice) and/or a proglacial lake (by 2.5 times vs land-terminating). The ten-fold acceleration in ice loss we have observed across the Himalaya far exceeds any centennial-scale rates of change that have been recorded elsewhere in the world.

Abstract Background Prior studies have suggested that preoperative dehydration increases odds of perioperative complications in several areas of orthopedic surgery. This study aimed to evaluate whether preoperative hydration status is associated with the incidence of short-term complications after primary total joint arthroplasty. Methods The 2012–2019 National Surgical Quality Improvement Program (NSQIP) database was used to explore the relationship between preoperative dehydration (ratio of preoperative BUN divided by preoperative Creatinine (BUN/Creatinine) > 20) and perioperative outcomes of total hip (THA) and total knee arthroplasty (TKA) patients. Univariate comparisons and multivariate regression analyses were conducted to identify specific complications that occurred more often in patients with preoperative dehydration. Results Of 188,629 THA and 332,485 TKA patients, 46.3 and 47.0% had preoperative dehydration, respectively. After controlling for demographics and comorbidities, dehydrated THA patients were no more likely to experience a complication compared to their non-dehydrated counterparts (relative risk [RR] = 0.97, 99.7% Confidence Interval [CI]: 0.92–1.03, P = 0.138) nor increased risk of blood transfusion (RR = 1.02, CI = 0.96–1.08, P = 0.408). Similar to THA patients, dehydrated TKA patients were not more likely to have a complication after surgery (RR = 0.97, CI = 0.92–1.03, P = 0.138) and were at no greater risk of transfusion (RR = 1.02, CI = 0.96–1.07, P = 0.408). A sub-analysis covering only patients with BUN and Cr values determined within 24 h after surgery was performed and similarly found no significant increase in perioperative complications or transfusion. Conclusion Overall, preoperative dehydration in patients undergoing THA/TKA did not appear to increase risk of transfusion or other perioperative complications. Further research is needed to characterize the role of hydration prior to elective total joint arthroplasty.

Background: Achondroplasia is the most common skeletal dysplasia, and total joint arthroplasty of the hip and/or knee in this patient population may present unique challenges. Methods: All patients undergoing primary total hip or total knee arthroplasty (THA or TKA) for osteoarthritis in the 2010-2019 PearlDiver Mariner administrative database with least 90 days of postoperative follow-up were identified. Those with achondroplasia were matched 1:10 to patients without achondroplasia based on age, sex, and medical comorbidities. Ninety-day adverse events were assessed and compared using multivariate logistic regression. Five-year implant survival was determined and compared with Kaplan-Meier implant survival curves. Significance was set at P < .05. Results: For THA, 150 patients with achondroplasia were matched to 1484 patients without and had significantly higher 90 days odds of surgical site infection (odds ratio [OR] = 3.49, P = .005) and readmission (OR = 2.35, P = .016). For TKA, 285 patients with achondroplasia were matched to 2828 without and had higher odds of aggregated any adverse event (OR = 1.52, P = .006) and transfusion (OR = 2.31, P < .001). Rates of the other studied adverse events were not significant for either set of the analyses. At 5 years, implant survival for those with and without achondroplasia was not different for those undergoing THA (P = .321) or TKA (P = .910). Conclusions: The present study represents the largest cohort of patients with achondroplasia undergoing total joint arthroplasty to date. Although several short-term adverse events had greater odds for those with achondroplasia, 5-year survival was not different for those with or without achondroplasia after THA or TKA, supporting confidence in longer term implant success.

Abstract Aldosterone exerts some of its effects not by binding to mineralocorticoid receptors, but rather by acting via G protein‐coupled estrogen receptors (GPER). To determine if aldosterone binds directly to GPER, we studied the ability of aldosterone to compete for the binding of [3H] 2‐methoxyestradiol ([3H] 2‐ME), a high potency GPER‐selective agonist. We used GPER gene transfer to engineer Sf9‐cultured insect cells to express GPER. We chose insect cells to avoid interactions with any intrinsic mammalian receptors for aldosterone. [3H] 2‐ME binding was saturable and reversible to a high‐affinity population of receptors with Kd = 3.7 nM and Bmax = 2.2 pmol/mg. Consistent with agonist binding to G Protein‐coupled receptors, [3H] 2‐ME high‐affinity state binding was reduced in the presence of the hydrolysis‐resistant GTP analog, GppNHp. [3H] 2‐ME binding was competed for by the GPER agonist G1, the GPER antagonist G15, estradiol (E2), as well as aldosterone (Aldo). The order of potency for competing for [3H] 2‐ME binding, namely 2ME > Aldo > E2 ≥ G1, paralleled the orders of potency for inhibition of cell proliferation and inhibition of ERK phosphorylation by ligands acting at GPER. These data confirm the ability of aldosterone to interact with the GPER, consistent with the interpretation that aldosterone likely mediates its GPER‐dependent effects by direct binding to the GPER. Significance statement Despite the growing evidence for aldosterone's actions via G protein‐coupled estrogen receptors (GPER), there remains significant skepticism that aldosterone can directly interact with GPER. The current studies are the first to demonstrate directly that aldosterone indeed is capable of binding to the GPER and thus likely mediates its GPER‐dependent effects by direct binding to the receptor.

Anthropogenic stressors such as climate warming and invasive species and natural stressors such as parasites exert pressures that can interact to impact the function of ecosystems. This study investigated how these stressors interact to impact the vital ecosystem process of shredding by keystone species in temperate freshwater ecosystems. We compared metabolic rates and rates of shredding at a range of temperatures up to extreme levels, from 5 °C to 30 °C, between invasive and native amphipods that were unparasitised or parasitised by a common acanthocephalan, Echinorhynchus truttae. Shredding results were compared using the relative impact potential (RIP) metric to investigate how they impacted the scale with a numerical response. Although per capita shredding was higher for the native amphipod at all temperatures, the higher abundance of the invader led to higher relative impact scores; hence, the replacement of the native by the invasive amphipod is predicted to drive an increase in shredding. This could be interpreted as a positive effect on the ecosystem function, leading to a faster accumulation of amphipod biomass and a greater rate of fine particulate organic matter (FPOM) provisioning for the ecosystem. However, the high density of invaders compared with natives may lead to the exhaustion of the resource in sites with relatively low leaf detritus levels.

Background: Owing to COVID-19, arthroplasty fellowship programs will be required to interview virtually for the current application cycle. Unrelated to COVID-19, our arthroplasty fellowship offered the 2019-2020 interviewees the option of an in-person or virtual interview. The purpose of the present study is to compare interviewee perceptions regarding in-person vs virtual interview formats from that application cycle at a single institution. Methods: A 17-question survey was sent to all 26 interviewees (13 in-person and 13 virtual) shortly after the rank-list submission deadline. Interviewees were asked to what extent they agreed or disagreed with several statements, ranging from whether the interview was enjoyable to whether interviewees felt they were being adequately evaluated. In this Likert scale rating system, “strongly agree” was given 5 points (more positive outlook), and “strongly disagree” was given 1 point (more negative outlook). Chi-square analyses were performed. Results: Seventeen interviewees (8 in-person and 9 virtual) returned questionnaires (response rate: 65%). Both in-person and virtual interview ratings were similar when averaged across all statements (4.5 vs 4.4, P = .67). In-person and virtual ratings were also similar for each individual statement (all P > .05). On average, interviewees spent $557/in-person interview. Fifteen (88%) said virtual interviews were more convenient, and 14 (94%) said they were more cost-effective. Conclusion: At a single institution, perceptions on interview format, as quantified through Likert scale ratings, were similar between in-person and virtual groups. The vast majority also viewed virtual interviews as more convenient and cost-efficient. These findings have immediate implications for future fellowship application cycles.

Abstract Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.