1H Spin-Lattice Relaxation Processes in Solutions of H2N-Fe3O4 Nanoparticles: Insights from NMR Relaxometry.

1H spin-lattice relaxation experiments have been performed for water and glycerol/water solutions of H2N-Fe3O4 superparamagnetic nanoparticles (NPs) of about 7 nm diameter. The experiments encompass a broad frequency range covering 3 orders of magnitude, from 10 kHz to 10 MHz (referring to 1H resonance frequency), and have been performed in the temperature range from 298 to 313 K, varying the concentration of the superparamagnetic species. This extensive dataset has been used for twofold purposes. The first one is to serve as a challenge for thorough tests of theoretical models describing nuclear relaxation in solutions of superparamagnetic NPs, depending on their magnetic properties and dynamics of the solvent molecules. The challenge is posed by the wish to reproduce the data in a broad range of magnetic fields (not only at high fields) and by the need to explain the differences in the relaxation scenarios for water and glycerol/water solutions by varying only the solvent parameters. The second purpose is to get insights into the magnetic properties (electronic relaxation properties) of the nanoparticles due to their high applicational potential.

Links between energy budgets, somatic condition, and life history reveal heterogeneous energy management tactics in a group-living mesocarnivore.

BACKGROUND: Optimal management of voluntary energy expenditure is crucial to the survival and reproductive success of wild animals. Nevertheless, a growing appreciation of inter-individual variation in the internal state driving movement suggests that individuals may follow different, yet equally optimal tactics under the same environmental conditions. However, few studies in wild populations have investigated the occurrence and demographic context of different contemporaneous energetic expenditure tactics. Here, we explore this neglected aspect of energy budgeting in order to determine the effect of life-history traits such as age and reproductive status on the co-occurrence of different energy-budgeting tactics in wild populations. METHODS: We investigated inter-individual heterogeneity in energy expenditure within a wild population of European badgers (Meles meles) by quantifying individual overall dynamic body acceleration (ODBA, from tri-axial accelerometry collars) and total daily energy expenditure (DEE, from doubly-labelled water) during 6-9 day deployments and dosing periods over six different seasons (spring, summer, and autumn) in 2018-2019. We obtained ODBA values for 41 deployments (24 unique badgers) and DEE measurements for 41 dosings (22 unique badgers). We then evaluated correlations between these energetic metrics and computed individual ratios of ODBA/DEE as a proxy for the proportion of total energy spent on activity. We measured the impact of alternative ODBA/DEE ratios on body condition, and use survival models constructed using 29 years of demographic data from the same population to situate body-condition changes in the context of age and reproductive status. RESULTS: Both ODBA and DEE were highly variable between individuals and exhibited season-specific relationships with individual body condition and life-history factors. DEE scaled allometrically with body weight, but only in summer and autumn; post-reproductive female badgers were lighter than other badgers during the spring but expended on average 350 kJ/day more than predicted from allometric scaling. Older badgers expended significantly less energy on movement during the summer than did younger adults. The ratio of ODBA to DEE (OD) provides a measure of proportional investment into movement. This ratio correlated more significantly with next-season body condition than either energetic metric did independently. However, the majority of individuals with high OD ratios were either younger badgers or reproductive females, for which lower body condition typically presented less of a mortality risk in previous analyses of this population. CONCLUSIONS: Within a single population under the same environmental conditions, we found wide inter-individual variation in both mechanical and total energy expenditure. The adoption of different tactics aligns with relationships between life-history parameters and mortality risk previously studied within the population. Crucially, younger badgers and reproductive females appeared able to tolerate energy expenditure tactics that depleted their body condition more than other badgers. These findings provide a mechanism by which differences in individual energetic context set by life history can maintain heterogeneity in wild populations, providing a wide range of potential energetic tactics under changing environmental conditions.

Analgesic efficacy of surgeon placed paravertebral catheters compared with thoracic epidural analgesia after Ivor Lewis esophagectomy: a retrospective non-inferiority study.

Background: The Ivor Lewis esophagectomy is an operation that involves a laparotomy and a right thoracotomy, both of which are associated with severe postoperative pain and subsequent impairment of respiratory function. Currently, the accepted "gold standard" for postoperative analgesia for laparotomies and thoracotomies is the thoracic epidural. A systematic review has shown paravertebral blocks to be equivalent to epidural analgesia for post-thoracotomy pain control and have decreased incidence of nausea and vomiting, hypotension and respiratory depression. To our knowledge, the use of the paravertebral catheter (PVC) in open Ivor Lewis esophagectomy has not been formally studied. The primary outcome is the area under the curve (AUC) pain scores in the first 48 hours after surgery. Methods: We performed a retrospective chart review of the open Ivor Lewis esophagectomy patients at our local institution, with local research ethics board (REB) approval. Results: A total of 92 patients were included in this study: 43 patients had a PVC and 49 had a thoracic epidural for postoperative pan control. Overall, the PVC group was non-inferior and statistically equivalent to the epidural group. Time to ambulation in the PVC group was non-inferior compared to epidurals. The PVC group was superior when comparing total opioid consumption. Conclusions: Our retrospective study continues to challenge the role of epidurals as the gold standard of pain control post thoracotomy and laparotomy. Further prospective studies with a larger population are needed to better compare the two modalities.

Counter-strategies to infanticide: The importance of cubs in determining lion habitat selection and social interactions.

Animal social and spatial behaviours are inextricably linked. Animal movements are driven by environmental factors and social interactions. Habitat structure and changing patterns of animal space use can also shape social interactions. Animals adjust their social and spatial behaviours to reduce the risk of offspring mortality. In territorial infanticidal species, two strategies are possible for males: they can stay close to offspring to protect them against rivals (infant-defence hypothesis) or patrol the territory more intensively to prevent rival intrusions (territorial-defence hypothesis). Here, we tested these hypotheses in African lions (Panthera leo) by investigating how males and females adjust their social and spatial behaviours in the presence of offspring. We combined datasets on the demography and movement of lions, collected between 2002 and 2016 in Hwange National Park (Zimbabwe), to document the presence of cubs (field observations) and the simultaneous movements of groupmates and competitors (GPS tracking). We showed a spatial response of lions to the presence of offspring, with females with cubs less likely to select areas close to waterholes or in the periphery of the territory than females without cubs. In contrast, these areas were more selected by males when there were cubs in the pride. We also found social responses. Males spent more time with females as habitat openness increased but the presence of cubs in the pride did not influence the average likelihood of observing males with females. Furthermore, rival males relocated further after an encounter with pride males when cubs were present in the prides, suggesting that the presence of cubs leads to a more vigorous repulsion of competitors. Males with cubs in their pride were more likely to interact with male competitors on the edge of the pride's home range and far from the waterholes, suggesting that they are particularly assiduous in detecting and repelling rival males during these periods. In general, the strategies to avoid infanticide exhibited by male lions supported the territorial-defence hypothesis. Our study contributes to answer the recent call for a behavioural ecology at the spatial-social interface.

Projected development in Borneo and Sumatra will greatly reduce connectivity for an apex carnivore.

The islands of Borneo and Sumatra are strongholds for biodiversity and home for many endemic species. They also have experienced amongst the highest deforestation rates globally. Both islands are undergoing massive, rapid infrastructure development, leading to further deforestation and habitat fragmentation. Here, we identify priority areas for continued functional forest connectivity across Borneo and Sumatra, using spatial models of clouded leopard (Neofelis diardi, a forest indicator species) movement, and impacts thereto from existing and future infrastructure development. We specifically measure and map the anticipated impacts on forest functional connectivity of three major infrastructure development projects (Pan Borneo Highway, Trans-Sumatran Toll Road, and the new Indonesian capital city of Nusantara). We found that core clouded leopard habitats are already highly fragmented in Sumatra, constituting only ∼13 % of the island, with potential dispersal corridors still linking some habitat fragments. In Borneo, clouded leopard core habitats cover 34 % of the island, with one large central core area and several much smaller satellite cores, which are largely unprotected (15 % protected, compared to 42 % in Sumatra). The largest negative effect on habitat connectivity was predicted for Nusantara (66 % of the total connectivity loss predicted for all three infrastructure projects), reverberating across the entirety of Borneo with the strongest effects in East Kalimantan. The Pan Borneo Highway accounted for 28 % of the total connectivity loss, affecting every province in Borneo and Brunei, with 6 % of this decrease located within protected areas. The Trans-Sumatran Toll Road had the smallest negative effect on connectivity (6 %) but only when excluding the already built segments, which, when included, produce a total negative impact similar to that of the Pan Borneo Highway.

Baseline Measures of Physical Activity and Function Do Not Predict Future Fall Incidence in Sedentary Older Adults: A Prospective Cohort Study.

Physical activity (PA) and physical function (PF) are modifiable risk factors for falls in older adults, but their ability to predict future fall incidence is unclear. The purpose of this study was to determine the predictive ability of baseline measures of PA, PF, and lower limb strength on future falls. A total of 104 participants underwent baseline assessments of PA, PF, and lower limb strength. Falls were monitored prospectively for 12 months. Eighteen participants fell at least once during the 12-month follow-up. Participants recorded almost exclusively sedentary levels of activity. PA, PF, and lower limb strength did not differ between fallers and nonfallers. Twelve participants, who reported a minor musculoskeletal injury in the past 6 months, experienced a fall. The results of this study suggest that in a cohort of highly functioning, sedentary older adults, PA does not distinguish fallers from nonfallers and that the presence of a recent musculoskeletal injury appears to be a possible risk factor for falling.

Getting to the Meat of It: The Effects of a Captive Diet upon the Skull Morphology of the Lion and Tiger.

Zoo animals are crucial for conserving and potentially re-introducing species to the wild, yet it is known that the morphology of captive animals differs from that of wild animals. It is important to know how and why zoo and wild animal morphology differs to better care for captive animals and enhance their survival in reintroductions, and to understand how plasticity may influence morphology, which is supposedly indicative of evolutionary relationships. Using museum collections, we took 56 morphological measurements of skulls and mandibles from 617 captive and wild lions and tigers, reflecting each species' recent historical range. Linear morphometrics were used to identify differences in size and shape. Skull size does not differ between captive and wild lions and tigers, but skull and mandible shape does. Differences occur in regions associated with biting, indicating that diet has influenced forces acting upon the skull and mandible. The diets of captive big cats used in this study predominantly consisted of whole or partial carcasses, which closely resemble the mechanical properties of wild diets. Thus, we speculate that the additional impacts of killing, manipulating and consuming large prey in the wild have driven differentiation between captive and wild big cats.

Association between P-pulmonale and respiratory morbidity in COPD: a secondary analysis of the BLOCK-COPD trial.

RATIONALE: Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms. OBJECTIVE: We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH. METHODS: ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ). RESULTS: We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45-5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77-1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32-6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61). CONCLUSIONS: In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.

Mitigating Human Impacts on Wild Animal Welfare.

Human activities negatively impact the welfare of wild vertebrates in many different contexts globally, and countless individual animals are affected. Growing concern for wild animal welfare, especially in relation to conservation, is evident. While research on wild animal welfare lags behind that focused on captive animals, minimising human-induced harm to wild animals is a key principle. This study examines examples of negative anthropogenic impacts on wild animal welfare, how these may be mitigated and what further research is required, including examples from wildlife management, biodiversity conservation, wildlife tourism and wildlife trade. Further, it discusses the relationship between animal welfare and biodiversity conservation, and synergies that may be achieved between these. Ultimately, it is discussed how the welfare of wild animals may be balanced with other priorities to ensure that welfare is afforded due consideration in interactions between people and wildlife.

Characterizing Subcortical Structural Heterogeneity in Autism.

Autism presents with significant phenotypic and neuroanatomical heterogeneity, and neuroimaging studies of the thalamus, globus pallidus and striatum in autism have produced inconsistent and contradictory results. These structures are critical mediators of functions known to be atypical in autism, including sensory gating and motor function. We examined both volumetric and fine-grained localized shape differences in autism using a large (n=3145, 1045-1318 after strict quality control), cross-sectional dataset of T1-weighted structural MRI scans from 32 sites, including both males and females (assigned-at-birth). We investigated three potentially important sources of neuroanatomical heterogeneity: sex, age, and intelligence quotient (IQ), using a meta-analytic technique after strict quality control to minimize non-biological sources of variation. We observed no volumetric differences in the thalamus, globus pallidus, or striatum in autism. Rather, we identified a variety of localized shape differences in all three structures. Including age, but not sex or IQ, in the statistical model improved the fit for both the pallidum and striatum, but not for the thalamus. Age-centered shape analysis indicated a variety of age-dependent regional differences. Overall, our findings help confirm that the neurodevelopment of the striatum, globus pallidus and thalamus are atypical in autism, in a subtle location-dependent manner that is not reflected in overall structure volumes, and that is highly non-uniform across the lifespan.

RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. METHODS: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0). RESULTS: We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment. CONCLUSION: The revised RANO 2.0 criteria refine response assessment in gliomas.

Falls and falls-related injuries in individuals with chronic ankle symptoms: a cross-sectional study.

BACKGROUND: Falls are a major public health concern globally. While falls are associated with osteoarthritis and persistent pain at the hip and knee, falls have not been investigated in people with chronic ankle symptoms. This study aimed to compare self-reported history of falls between adults with and without chronic ankle symptoms. Secondary aims were to compare concern about falling and balance confidence between groups, and to identify factors associated with falling. METHODS: A total of 226 participants (134 with chronic ankle pain and/or stiffness and 92 controls) participated in this cross-sectional case-control study. Participants completed an online questionnaire about falls in the past 12 months, injuries associated with falling, concern about falling, balance confidence, function, pain and multimorbidity. RESULTS: Eighty-six (64%) participants with chronic ankle symptoms and 24 (26%) controls reported at least one fall in the last 12 months (p < 0.001). Participants with chronic ankle symptoms reported more falls, more injurious falls, and more hospitalisations because of a fall than controls (p > 0.002). There was a small effect for lower balance confidence and higher concern about falling in symptomatic participants (standardised mean difference: 0.39-0.49; p > 0.017). Logistic regression analysis identified that falling was associated with the presence of ankle symptoms (3.08 (1.20, 7.92); p = 0.02) and concern about falling (odds ratio (95% confidence intervals): 1.13 (1.05, 1.23); p = 0.002). CONCLUSIONS: Falls and falls-related injuries are a problem in individuals with chronic ankle symptoms. The high falls occurrence and concern about falling in individuals with chronic ankle symptoms suggest the need for clinicians to assess these factors in this population.

Cone-beam computed tomographic reconstructions in the evaluation of maxillary impacted canines.

Purpose: Prior to cone-beam computed tomography (CBCT), orthodontic competence included radiological interpretation. Nevertheless, maxillary impacted canines (MICs), because of their position and adjacent complex anatomy, have been challenging to interpret, particularly with regard to root resorption. Although CBCT cross-sectional reconstructions of MICs yielded clearer insights into its diagnosis and treatment planning, the value of simultaneously using 2 different cross-sectional or multiplanar reconstructions of the CBCT datasets - orthogonal and curved/panoramic multiplanar reconstructions - has hitherto not been considered. Materials and Methods: Both orthogonal and curved/panoramic multiplanar reconstruction series of 5 screenshots were each reconstructed from the 5 cm × 5 cm CBCT datasets of 15 separate MICs. Fifteen credentialled and experienced orthodontist volunteers reviewed 2 separate PowerPoints of 15 randomized series each, 1 week apart. Their review considered 6 factors that could affect treatment: the position and level of the MIC, the presence or absence of root resorption, ankylosis, cysts, and dilaceration. Results: All 15 orthodontists were statistically similar regarding overall years of experience and of CBCT use. Although either reconstruction alone allowed the orthodontists to determine whether ankylosis and, to a lesser extent, most of the other features were present or absent in the MIC, reviewing both reconstructions together was necessary to determine whether root resorption was present or absent in the adjacent tooth. Conclusion: Reviewing both orthogonal and curved/panoramic multiplanar reconstructions was necessary to evaluate the presence or absence of root resorption in the teeth adjacent to MICs and that of many other features.

Female-biased introductions produce higher predicted population size and genetic diversity in simulations of a small, isolated tiger (Panthera tigris) population.

Isolation of wildlife populations represents a key conservation challenge in the twenty-first century. This may necessitate consideration of translocations to ensure population viability. We investigated the potential population and genetic trajectory of a small, isolated tiger (Panthera tigris) population in Thailand's Dong Phayayen-Khao Yai forest complex across a range of scenarios. Using an individual-based, spatially-explicit population modelling approach, we simulate population and genetic trajectories and evaluate the relative impact of translocations from a related population. Population and genetic trajectories in our study were most sensitive to sex and number of individuals translocated and translocation frequency. Translocation of females produced consistently higher population, allelic richness, and heterozygosity compared to equal numbers of males. Despite population increases, declines in allelic richness and heterozygosity across simulations were stark, with simulations predicting a mean decline of allelic richness and heterozygosity of 46.5% and 53.5% without intervention, respectively. Translocations of four females every generation or every other generation were required to prevent substantial heterozygosity declines. While translocations could increase population size, they may fail to prevent long-term loss of genetic diversity in small populations unless applied frequently. This reinforces the importance of incorporating realistic processes of genetic inheritance and gene flow in modelling small populations.

Bilirubin-associated single nucleotide polymorphism (SNP) and respiratory health outcomes: a mendelian randomization study.

BACKGROUND: Observational studies have shown an association between higher bilirubin levels and improved respiratory health outcomes. Targeting higher bilirubin levels has been proposed as a novel therapeutic strategy in COPD. However, bilirubin levels are influenced by multiple intrinsic and extrinsic factors, and these observational studies are prone to confounding. Genetic analyses are one approach to overcoming residual confounding in observational studies. OBJECTIVES: To test associations between a genetic determinant of bilirubin levels and respiratory health outcomes. METHODS: COPDGene participants underwent genotyping at the baseline visit. We confirmed established associations between homozygosity for rs6742078 and higher bilirubin, and between higher bilirubin and decreased risk of acute respiratory events within this cohort. For our primary analysis, we used negative binomial regression to test associations between homozygosity for rs6742078 and rate of acute respiratory events. RESULTS: 8,727 participants (n = 6,228 non-Hispanic white and 2,499 African American) were included. Higher bilirubin was associated with decreased rate of acute respiratory events [incidence rate ratio (IRR) 0.85, 95% CI 0.75 to 0.96 per SD increase in bilirubin intensity]. We did not find significant associations between homozygosity for rs6742078 and acute respiratory events (IRR 0.94, 95% CI 0.70 to 1.25 for non-Hispanic white and 1.09, 95% CI 0.91 to 1.31 for African American participants). CONCLUSIONS: A genetic determinant of higher bilirubin levels was not associated with better respiratory health outcomes. These results do not support targeting higher bilirubin levels as a therapeutic strategy in COPD.

Cardiovascular Autonomic Function and Incident Chronic Obstructive Pulmonary Disease Hospitalizations in Atherosclerosis Risk in Communities.

Rationale: The autonomic nervous system extensively innervates the lungs, but its role in chronic obstructive pulmonary disease (COPD) outcomes has not been well studied. Objective: We assessed relationships between cardiovascular autonomic nervous system measures (heart rate variability [HRV] and orthostatic hypotension [OH]) and incident COPD hospitalization in the multicenter ARIC (Atherosclerosis Risk In Communities) study. Methods: We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals between baseline (1987-1989) autonomic function measures (HRV measures from 2-minute electrocardiograms and OH variables) and incident COPD hospitalizations through 2019. Adjusted analyses included demographic data, smoking status, lung function, comorbidities, and physical activity. We also performed analyses stratified by baseline airflow obstruction. Results: Of the 11,625 participants, (mean age, 53.8 yr), 56.5% were female and 26.3% identified as Black. Baseline mean percentage predicted forced expiratory volume in 1 second was 94 ± 17% (standard deviation), and 2,599 participants (22.4%) had airflow obstruction. During a median follow-up time of 26.9 years, there were 2,406 incident COPD hospitalizations. Higher HRV (i.e., better autonomic function) was associated with a lower risk of incident COPD hospitalization. Markers of worse autonomic function (OH and greater orthostatic changes in systolic and diastolic blood pressure) were associated with a higher risk of incident COPD hospitalization (hazard ratio for the presence of OH, 1.5; 95% confidence interval, 1.25-1.92). In stratified analyses, results were more robust in participants without airflow obstruction at baseline. Conclusions: In this large multicenter prospective community cohort, better cardiovascular autonomic function at baseline was associated with a lower risk of subsequent hospitalization for COPD, particularly among participants without evidence of lung disease at baseline.

Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.

Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas.

Analyzing the value of IONM as a complex intervention: The gap between published evidence and clinical practice.

OBJECTIVE: Intraoperative neurophysiological monitoring (IONM) was investigated as a complex intervention (CI) as defined by the United Kingdom Medical Research Council (MRC) in published studies to identify challenges and solutions in estimating IONM's effects on postoperative outcomes. METHODS: A scoping review to April 2022 of the influence of setting on what was implemented as IONM and how it influenced postoperative outcomes was performed for studies that compared IONM to no IONM cohorts. IONM complexity was assessed with the iCAT_SR tool. Causal graphs were used to represent this complexity. RESULTS: IONM implementation depended on the surgical procedure, institution and/or surgeon. "How" IONM influenced neurologic outcomes was attributed to surgeon or institutional experience with the surgical procedure, surgeon or institutional experience with IONM, co-interventions in addition to IONM, models of IONM service delivery and individual characteristics of the IONM provider. Indirect effects of IONM mediated by extent of tumor resection, surgical approach, changes in operative procedure, shorter operative time, and duration of aneurysm clipping were also described. There were no quantitative estimates of the relative contribution of these indirect effects to total IONM effects on outcomes. CONCLUSIONS: IONM is a complex intervention whose evaluation is more challenging than that of a simple intervention. Its implementation and largely indirect effects depend on specific settings that are usefully represented in causal graphs. SIGNIFICANCE: IONM evaluation as a complex intervention aided by causal graphs and multivariable analysis could provide a valuable framework for future study design and assessments of IONM effectiveness in different settings.

Local intensity of artisanal gold mining drives mercury accumulation in neotropical oxbow lake fishes.

Driven by surges in global gold prices and additional socio-economic factors, artisanal small-scale gold mining (ASGM) in the Global South is increasing and driving emissions of significant quantities of mercury (Hg) into the air and freshwater. Hg can be toxic to animal and human populations and exacerbate the degradation of neotropical freshwater ecosystems. We examined drivers of Hg accumulation in fish that inhabit oxbow lakes of Peru's Madre de Dios, a region with high biodiversity value and increasing human populations that depend on ASGM. We hypothesized that fish Hg levels would be driven by local ASGM activities, by environmental Hg exposure, by water quality, and by fish trophic level. We sampled fish in 20 oxbow lakes spanning protected areas and areas subject to ASGM during the dry season. Consistent with previous findings, Hg levels were positively associated with ASGM activities, and were higher in larger, carnivorous fish and where water had lower dissolved oxygen levels. In addition, we found a negative relationship between fish mercury levels associated with ASGM and the occurrence of the piscivorous giant otter. The link between fine-scale quantification of spatial ASGM activity and Hg accumulation, as indicated by the result that in the lotic environment, localized effects of gold mining activities are stronger drivers (77 % model support) of Hg accumulation than environmental exposure (23 %) constitutes a novel contribution to a growing body of literature on Hg contamination. Our findings provide additional evidence of high Hg exposure risks to neotropical human and top carnivore populations subject to the impacts of ASGM, which depend on freshwater ecosystems undergoing gradual degradation. The documented spatial variation in Hg accumulation and increased Hg levels in carnivorous fish should serve as a warning to human communities in Madre de Dios to avoid the proximity of high-intensity gold mining areas and minimize local carnivorous fish consumption.